Anatomy and Embryology

, Volume 207, Issue 6, pp 417–437

A re-evaluation of the premaxillary bone in humans


    • Abteilung für Anatomie und Embryologie, Institut für AnatomieRuhr-Universität Bochum
  • M. Jacob
    • Abteilung für Anatomie und Embryologie, Institut für AnatomieRuhr-Universität Bochum

DOI: 10.1007/s00429-003-0366-x

Cite this article as:
Barteczko, K. & Jacob, M. Anat Embryol (2004) 207: 417. doi:10.1007/s00429-003-0366-x


The discovery of the premaxillary bone (os incisivum, os intermaxillare or premaxilla) in humans has been attributed to Goethe, and it has also been named os Goethei. However, Broussonet (1779) and Vicq d’Azyr (1780) came to the same result with different methods. The first anatomists described this medial part of the upper jaw as a separate bone in the vertebrate skull, and, as we know, Coiter (1573) was the first to present an illustration of the sutura incisiva in the human. This fact, and furthermore its development from three parts:—(1) the alveolar part with the facial process, (2) the palatine process, and (3) the processus Stenonianus—can no longer be found in modern textbooks of developmental biology. At the end of the nineteenth and in the early twentieth century a vehement discussion focused on the number and position of its ossification centers and its sutures. Therefore, it is hard to believe that the elaborate work of the old embryologists is ignored and that the existence of a premaxillary bone in humans is even denied by many authors. Therefore this re-evaluation was done to demonstrate the early development of the premaxillary bone using the reconstructions of Felber (1919), Jarmer (1922) and data from our own observations on SEM micrographs and serial sections from 16 mm embryo to 68 mm fetus. Ossification of a separate premaxilla was first observed in a 16 mm embryo. We agree with Jarmer (1922), Peter (1924), and Shepherd and McCarthy (1955) that it develops from three anlagen, which are, however, not fully separated. The predominant sutura incisiva (rudimentarily seen on the facial side in a prematurely born child) and a shorter sutura intraincisiva argue in this sense. The later growth of this bone and its processes establish an important structure in the middle of the facial skull. Its architecture fits well with the functional test of others. We also focused on the relation of the developing premaxilla to the forming nasal septum moving from ventral to dorsal and the intercalation of the vomer. Thus the premaxilla acts as a stabilizing element within the facial skeleton comparable with the keystone of a Roman arch. Furthermore, the significance of the premaxillary anlage for the closure of the palatine was documented by a synopsis made from a stage 16, 10.2 mm GL embryo to a 49 mm GL fetus. Finally the growth of the premaxilla is closely related to the development of the human face. Abnormal growth may be correlated to characteristic malformations such as protrusion, closed bite and prognathism. Concerning the relation of the premaxillary bone to cleft lip and palate we agree with others that the position of the clefts is not always identical with the incisive suture. This is proved by the double anlagen of an upper–outer incisor in a 55 mm fetus and an adult.


Architecture of craniofacial regionHistoryHuman embryosPremaxillary bone developmentSutures


In the development of the human craniofacial morphology, a special part of the palate maxilla nose region—the premaxillary bone (os incisivum, os intermaxillare, os Goethei, Zwischenkiefer)—plays an essential role. According to developmental biologist, the anlagen of this bone belong to the primary palate (Peter 1911, 1913, 1924; Hochstetter 1949, 1955). It contains the alveolar ridge of the four upper incisors, and was observed in animals by Galen (cited by Vacher et al. 2001a) due to sutures delimiting the secondary palate, maxillary, nasal and frontal bones; however, Vesalius 1538 (in Gysel 1993) neglected a special bone for man. The discovery of this bone in humans was related to Goethe (1784, see for references Bräuning-Oktavio 1956). Yet other earlier reports do exist.

In actual textbooks of embryology, if mentioned, the premaxillary bone is illustrated in relation to the facial and palatine development in a lingual view, showing an at first bipartite, then fused trapezoid and finally a wedge-shaped horizontal body, which is rostrally intercalated into the two palatine halves of the maxillary. Today the frontal, as well as the nasal processes (crista nasalis or processus Stenonianus after Jarmer 1922, prevomerine center after Fawcett 1911, or os praevomerale after Wegner in Peter 1924) with the foramen incisivum are ignored.

Likewise illustrations in osteological atlases show only the nasal and lingual side with the corresponding suture. There is no demonstration of the frontal process which fuses with the maxillary bone facially and which punctually attaches itself to the frontal bone.

Not only the number of ossification centers of maxillary and/or premaxillary bone is controversial (Kölliker Th. 1882, 1888; Felber 1910; Jarmer 1922; Peter 1924; Chase 1942; Woo 1949; Shephard and McCarthy 1955; Kraus and Decker 1960; Vacher et al. 1999, 2001a and others), but even the existence of a separate anlage has been questioned (Fawcett 1911; Eschler 1966; Wood et al. 1967; Vacher et al. 1999, 2001a, 2001b).

We therefore designed this article: (1) to discuss that, Goethe cannot be considered as the first discoverer of the “Zwischenkiefer” in humans; (2) to demonstrate, that the premaxilla develops in man as a separate three-dimensional structure composed of three different parts. In this point we especially refer to two nearly forgotten investigators, Felber (1919) and Jarmer (1922) with their plastic reconstructions, illustrating origin and development of the “Zwischenkiefer” element, and their own serial sections of embryos from 16 mm to 68 mm; (3) to show that the premaxilla exert an important function as a vertical stabilization element in the architecture of the facial skeleton, including all four upper incisors; (4) to consider the premaxillary bone development in relation to the movement of the nasal septum during the fusion of the secondary palate; (5) to analyze data from the literature and own embryos concerning the association of the premaxillary bone to the primary facial processes and thus to the location of alveolar clefts.

Part I

History regarding the discovery of the intermaxillary bone in humans

The discussion about the existence of a separate intermaxillary bone in humans seems to be nearly as old as the history of comparative anatomy. The first known description of this bone can be dated back to Galen (131–200) (see for details Franz 1933; Ashley-Montagu 1936) in animals. Vesalius (1543, in Gysel 1993), however, denied the existence of such an independent bone in humans. Since then, the intermaxillary bone (“Zwischenkiefer”) became a central place in the discussion of dissimilarity or homology between men and other vertebrates. Thus, in the concept of Camper 1778 (cited by Bräuning-Oktavio 1956) the division of maxilla “entre la dent incisoire et la canine” is considered to be a main difference between ape and man. In this context Goethe’s discovery of the “Zwischenkiefer” at the human skull has to be valuated. Its historical circumstances are precisely investigated and described by Bräuning-Oktavio (1956). According to Goethe, accident and reflection had guided him in his research on several skulls of animals and men. It is not only the anatomical discovery that has made the work of Goethe so famous and important, but it was Goethe’s idea of a common type—harmonia naturae (Typus, Bauplan)—of the vertebrate body that contradicted against a special position of men (Goerttler 1950).

Goethe started his morphological studies in 1781 as a student of his friend Loder, professor of anatomy in Jena (Figs. 1a, b). His first tracts about the intermaxillary bone were published 1784/1786 (see for references Franz 1933); one new edition appeared in 1981. In Voss (1979) an extract from Goethe’s letters can be read:
Fig. 1 a

J.W. v. Goethe (1749–1832) at 36 years, about the age when he described the intermaxillary bone. b J.Ch. Loder (1753–1832), great anatomist of his time, friend and consulter of Goethe. c Volcher Coiter (1534–1576), the first anatomist who presented an illustration of the sutura incisiva in humans. References of pictures: a see under reference Richter K et al. (1985); b privately owned by M. Jacob, engraved by J.G. Müller, after a painting of F. Tischbein, printed by Heubach, Nuremberg at Johann Friedrich Frauenholz & Company, 1801; c copperplate, engraved by J.F. Leonart (1669) after a small painting

To Herder, 27th March 1784, “Ich habe gefunden—weder Gold noch Silber, aber was mir eine unsägliche Freude macht—das os intermaxillare am Menschen! Ich verglich mit Lodern Menschen- und Thierschädel, kam auf die Spur und siehe da ist es.” And to Mrs v. Stein the same day, “...ich habe eine anatomische Entdeckung gemacht die wichtig und schön ist.”

In the original paper, Loder was also helpful with the right terminology and the translation into Latin. Many years later (1819 and 1831) official “de luxe” editions were published.

According to Lubosch (1931), the early eighteenth century was the time of the first flowering of comparative anatomy and it was especially Vicq d’Azyr who—like Goethe—looked for similarities among the species. It was also Vicq d’Azyr who discovered (see for references Bräuning-Oktavio 1956) the intermaxillary bone, which he called os maxillaire antérieur, in the human fetus and presented his “Mémoires” at the Academy of Sciences in Paris 1780. Thus, it is the latter to whom the priority in this research field is due, even if both Goethe and Vicq d’Azyr came independently and with different methods to similar results. Beyond that, in 1779, Broussonet (cited by Bräuning-Oktavio 1956) read his first “Mémoire” about the teeth and the intermaxillary bone, yet an official edition of his work appeared later in 1789. Nevertheless Vicq d’Azyr did not cite him and required the priority. But Goethe surely learned about the work of Vicq d’Azyr from Loder, but never cited Vicq d’Azyr. Kohlbrugge 1913 (cited from Franz 1933) in his critical studies of Goethe’s scientific work, reproached him for holding back information.

In the nearly forgotten work of Volcher Coiter (1573, 1573/1955, Fig. 1c) (see also his biography in Herrlinger 1952) an illustration of the sutura incisiva can be found, although he only wrote “Superioris maxillae ossa ossibus adultorum figure, et numero, et situ respondent”.

Although Goethe was not the first to discover the premaxillary bone as again stated recently by Neddermeyer (2002). The great philosophical and ideological importance of this topic can be estimated by Rousseau’s (1858) treatise “de la non-existence de l’os intermaxillaire” arguing in the sense of Camper (see for references Franz 1933; Bräuning-Oktavio 1956). Thus the debate about this bone did not finish: Lawrence (1844) surgeon and comparative anatomist denied its existence in man, yet Leidy (1849) demonstrated the existence of intermaxillary bone in a 9 to 10 week-old human embryo. Likewise, Callender (1869) who investigated the ossification of the bones of the human face found that in a fetus of 4.3 inches “the intermaxilla completely formed and that it may be traced back as a distinct bone. In a fetus 9 inches long, either intermaxillary bone is in great part fused with its corresponding upper maxilla.” Interestingly he writes in his introduction that it was its purpose “to supply information regarding some few points with which we are yet imperfectly acquainted, such as the growth of the maxilla, and the formation and eventual obliteration of the intermaxillary bones.”

Even now we still find authors who deny a separate premaxilla (Wood et al. 1949; Vacher et al. 2001a, 2001b).

The development of the premaxilla

In the nineteenth and early twentieth century, the discussion about parts of the intermaxillary bone and its sutures was settled again with great vehemence and especially the controversy between Albrecht and Kölliker Th. is well reported (Inouye 1912).

The main discussion now focused on the number of ossification centers. The most important authors, in our view, to this topic are summarized as follows (based on data of Kräutler 1966):

One center of intermaxilla: Bruni (cited by Kräutler 1966), Felber 1919, Inouye 1912, Kölliker Th. 1882, 1888, Mall 1906, Merkel 1891.

Two centers of intermaxilla: Authenrieth 1879 (see for references Felber 1919; Inouye 1912), Albrecht 1879, 1884, v Bardeleben 1879, Biondi 1888, v. Meyer 1884, Thourén 1926 (cited by Kräutler 1966), Wallesch-Gladzinski 1995, Warynski 1888.

Three centers of intermaxilla: Jarmer 1922, Peter 1924, Shepherd and McCarthy 1955. See for further information Inouye 1912, Felber 1919, Peter 1924, Kräutler 1966.

According to Le Double (1906) in Bardeen (1910), some authors describe six or more centers (maxilla and premaxilla taken together). In the discussion of multiple ossification centers, Albrecht (1879) introduced a sutura intraincisiva, and Biondi (1888), a sutura intraalveolaris that are supposed to exist beside the generally accepted sutura incisiva and sutura palatina media.

A second heavily debated question was from which facial processes the intermaxillary bone derives. Kölliker Th. (1882, 1888) named only the tissue of the medial nasal process as the source. According to Albrecht (1879), Warynski (1888) and v. Meyer (1884) the bone derives from the mesenchyme of the medial nasal and the maxillary process. Inouye (1912) and Jarmer (1922) even traced it back to the medial and lateral nasal and the maxillary process.

These opinions are closely related with the question of synonymy of the primary palate and intermaxillary bone on one hand, and the location of clefts in lip and palate on the other. Inouye (1912) could solve this problem by demonstrating, that the development of bones does not coincide with the primary development of the face. As a consequence the epithelial-fusion lines are not identical with the incisive fissure (Lisson and Kjaer 1997).

A three-dimensional figuration of the developing bone seems to be a good tool for a better understanding of its relationships. The elaborate graphic reconstructions of Jarmer (1922) on young human embryos and fetuses, and Felber’s graphic (1919) of 5 month-old fetuses are worth represented in a new modus.

Figure 2 shows the three stages of Jarmer (1922) 25 mm, up to 40 mm, from 40 mm: in a horizontal view.
Fig. 2a–c

Reconstruction of the bony anlagen within the palate/upper jaw in embryos at the age of 8 weeks, 25 mm (a), before 9 weeks, 40 mm (b), more than 9 weeks, 40 mm (c), according to Jarmer 1922. Bar 1 mm. 1 alveolar part of the premaxilla, 2 maxilla, 3 processus palatinus of premaxilla, 4 processus Stenonianus (1,3,4,8 region of the primary nasal floor according to Peter 1911, 1913), 5 palatine process of maxilla, 6 border between medial nasal process (fin) and lateral facial process, 7 primary palatine fissure, 8 processus globularis of medial nasal fin or primary palate, 9 secondary palatine fissure. * later sutura incisiva, within the dental anlage, i1 medial incisor, i2 lateral incisor, c canine, m molar, arrowheads border between alveolar part of premaxilla to alveolar part of the maxilla

(a) The 25 mm (eighth week) embryo exhibits the bony anlage of the alveolar part of the premaxilla already fused with the maxillary anlagen. The primary palate deriving from the medial nasal process is dedicated. Its border to the lateral facial processes is located more medially than the boundary between alveolar parts of premaxillary and maxillary anlage. We can conclude that the medial part of the maxillary process delivers material to the premaxilla.

(b) The 40 mm (ninth week) embryo shows the separate anlage of the palatine process that completes in the horizontal view the premaxillary bone.

(c) Greater than 40 mm: the palatine processes of the paired premaxillary bone are fused with the body of the premaxilla. Dorsal, a sutura incisiva reminds on the boundary between each palatine process of the premaxilla and the maxilla. Two little ovoid bones arise in the median plane, considered as anlage of processus Stenonianus, or spina and crista nasalis anterior.

Jarmer (1922) demonstrated that the intermaxillary bone belongs to all three facial processes, which form the primary nasal floor (Peter 1911, 1913, 1924; Hochstetter 1955). These observations have to be completed by studies of Felber (1919) showing reconstructions in a vertical view. He found a separate premaxillary ossification center in a 19.4 mm embryo (Fig. 3b, compare with a). Only few days later, the premaxillary and maxillary ossification centers have fused (Fig. 3c) and a processus frontalis of the premaxilla grows rostrad, a palatine process was not seen. In a medial or caudal view (not shown here), the latter can be found in an embryo of the ninth week (about 40 mm); however, not as a separate bone but connected by bridges of bones with the corpus of premaxilla. Basally, the frontal processes of both maxilla and premaxilla are fused whereas the upper parts remain separated by a suture (Fig. 3d). Thus we can distinguish three parts of the premaxilla: firstly the alveolar part with facial process, secondly the palatine process and thirdly the processus Stenonianus that fuses with the nasal cartilaginous septum and the vomer (see also Shepherd and McCarthy 1955).
Fig. 3a–d

Reconstruction of the right bony upper jaw of human embryos. a End of the sixth week, 16.5 mm; b beginning of the seventh week, 19.4 mm; c middle of the seventh week, 20.2 mm; d ninth week, straight line 41.5 mm, line of dorsum 62 mm, circumference of head 42 mm (according to Felber 1919). Bars a, b, c 0.5 mm; d 1 mm. *1 premaxillary ossification point, 1 premaxilla, *2 maxillary ossification point, 2 maxilla, 3 facial alveolar wall, 4 processus frontalis of maxilla, 5 processus frontalis of premaxilla, 6 dental ridge, 7 outer contour of medial nasal process, 8 outer contour of maxillary process, 9 nasolacrimal sulcus, 10 os palatinum, 11 part of the left premaxilla, 12 margin of the apertura piriformis, arrowhead sutura palatina, asterisks sutura incisiva

Simultaneously with these early stages of premaxillary bone development, the characteristic morphogenesis of the face starts by formation of both, the frontonasal process and the first pharyngeal arch (see for detail Hochstetter 1949, 1955; Hamilton et al. 1972; Hinrichsen 1985, 1990, 1991). The maxillary swelling of the first pharyngeal arch is then growing forward, and a medial and lateral nasal fold appears on each side of the nasal pit. The maxillary process fuses with the globular process of the medial nasal swelling, thus forming the primary nasal floor, which in the depth is also formed, by the lateral nasal processes (Peter 1911, 1913, 1924; Hinrichsen 1985, 1990; Hinrichsen and Jacob 1985). As seen in a 17.5 mm GL embryo at stage 19 (Fig. 4a, c, e), it is from this medial nasal process that a backward outgrowth forms the paired primitive palate the soft tissue corresponding to the palatine process of the intermaxillary bone. Similarly, the secondary palate is developed from the maxillary process. In the furrow between the primary and secondary palate, the choanae arises.
Fig. 4a–e

Schematic drawing competing the SEM micrographs (c, d). Views into the oral cavity of a stage 19 embryo, 17.5 mm GL (greatest length; see for definition O’Rahilly and Müller 1978), seventh week (a, c, e), and a stage 22 embryo, 26 mm GL, eighth week (b, d). Mandibular arch and floor of the mouth are removed. View from the lingual side. Note in a and c the position of the premaxillary bulge/primary palate ventral to the palatine shelves/secondary palate extending in a latero–medial as well as cranio-dorsal direction. e Detail of c with premaxillary anlage. Bars a, b 1 mm; c, d 0.5 mm, e 0.1 mm. 1 relief of paired (a) or fused (b) premaxillary anlage/primary palate, 2 secondary palate, 3 adenohypophysis/remnant of Rathke’s pouch, 4 roof of the oral cavity, 5 mandibular arch and floor of the oral cavity removed, 6 upper lip anlage, 7 nasal plug, * intermaxillary bulge at the ventral roof of oral cavity, short arrows choanae, arrowheads sutura incisiva between primary and secondary palate

At stage 22 (26 mm GL) the paired primary palate grows medially and fuses in the midline (Fig. 4b, d). The palate processes of the maxilla approach each other. As the demarcation between primary and secondary palate the sutura incisiva of the soft tissue can be considered (Fig. 4a). Its deeper prolongation is not identical with the bony sutures.

According to Hinrichsen (1991) the epithelial remnants indicating the fusion line of facial processes has disappeared first, in the frontal part of a stage 18 embryo (15 mm GL). The premaxillary ossification center appears shortly afterwards when fusion is completed at stage 18, 16 mm (see Fig. 6a). An exact correspondence between facial processes and bony anlagen do not exist, though the main part of the premaxilla arises within the medial nasal swelling.

In Figure 5 the ossification of the intermaxillary bone is projected within the face of a 27 mm-GL embryo (stage 23, eighth week) related on our own observations and data from literature.
Fig. 5

Projection of the left intermaxillary bone into the face of a stage 23 embryo, 27 mm GL eighth week. Bar 1 mm. 1 intermaxillary bone, 2 frontal process of maxilla with palatine bone

In our material, ossification of the premaxilla first appears in a 16 mm embryo from the seventh week (Fig. 6a) as an irregular formed core within dense mesenchyme. This bony anlage has an irregular shape, as if composed by confluence of several bony islands. The frontal section of a 19.5 mm embryo also reveals a spongy architecture of the first premaxillary bone lamella (Fig. 6b). In embryos of the eighth week, ramification of the thin bone lamella becomes evident (Fig. 6c, 22 mm). In sagittal sections a tri-directional extension especially an extension in frontal direction has taken place (Fig. 6d, 23 mm). In the 29 mm embryo (Fig. 6e), the alveolar parts of the premaxilla are still separated from each other by a broad median suture and from the maxillary bone by a thin sutura incisiva. The palatine processes of the premaxillary bones appear. The nasal septum is fused with the intermaxillary region.
Fig. 6a–e

Anlage of the premaxillary bone in young embryos. a Sagittal section of a 16 mm GL embryo, 10 μm, St. 18 CC, seventh week. The anlage of the premaxilla appears. b Frontal section of a 19.5 mm GL embryo, 8 μm, seventh week. c Frontal section of 22 mm GL embryo, 8 μm. d Sagittal section of a 23 mm GL embryo, 8 μm. e Frontal section of a 29-mm GL embryo, 10 μm, ce all eighth week p.c. Magnification: a ×220, b ×27, c ×70, d ×80, e ×25. 1 os incisivum pars alveolaris, 2 processus Stenonianus, 3 processus palatinus maxillae, 5 sutura incisiva, 11 palatine part of premaxilla, 13 N. nasopalatinus, 15 septum nasi, ◄ pieces of premaxillary bone

The prevomerine (processus Stenonianus) is clearly visible in sagittal sections of a 32 mm embryo as a third anlage but fine connections to the central part may exist (Fig. 7a–d). The N. nasopalatinus runs through this anlage (Fig. 7b, c) within the canalis incisivus. The palatine part of the premaxillary bone becomes more prominent in a 45 mm fetus as a bilaminar bone (Fig. 7e, f). In a 55 mm embryo (Fig. 7g, h) the more compact alveolar part surrounds the anlagen of the incisors while the prevomeral wings of the crista nasalis and the palatine part of the premaxilla have a spongy architecture. A sutura intraincisiva (Fig. 7a, b, d, e, f, h) still separates the palatine processes partly from the prevomerine part of premaxilla.
Fig. 7a–h

Sagittal sections of the median region of a 32 mm GL embryo, 8 μm, ninth week (a–d). c Enlarged detail of premaxilla in b. e 45 mm GL fetus, 10 μm, with a detail (f) of the palatine part of the premaxillary bone. Transversal sections of a 55 mm GL fetus, 10 μm, through the prevomeral wings (g) and the anlage of the palatinum and premaxilla (h). Magnification: a ×23; b ×60; c ×130; d ×52; e ×36; f ×25; g ×25. 1 Os incisivum pars alveolaris, 2 prevomerine part/proc. Stenonianus/os praevomerale, 3 processus palatinus maxillae, 4 lamina horizontalis ossis palatini, 5 sutura incisiva, 6 sutura palatina transversa, 7 vomer, 8 lip, 9 tongue, 10 foramen incisivum, 11 palatine part of premaxilla/os intermaxillare pars palatina, 13 N. nasopalatinus, 14 prevomeral wings of the crista nasalis, * sutura intraincisiva

A coherent spongy premaxillary bone is exhibited in a series of frontal sections from an 11-week fetus 68 mm GL (Fig. 8). The anlagen of teeth have appeared (Fig. 8a, b) and alveolae form within the maxilla and premaxilla. In Figure 8b, c, starting between the lateral incisor and the caninus, an oblique zone without ossification is found that represents the sutura incisiva and thus separates maxilla and premaxilla. This is in line with other studies e.g., Felber (1919). Wallesch-Gladzinski (1994) found even in older fetuses a broad sutura incisiva. The septum nasi contains a forked vomer that will fuse with the premaxillary bone (Fig. 8d) (compare Smith and Bhatnagar 2000). A broad sutura palatina mediana is still obvious.
Fig. 8a–d

Frontal sections of a 68 mm fetus, 10 μm, eleventh week, a-d from rostral to dorsal. Bars 1 mm. Note the anlagen of teeth. 1 i1 (dens incisivus medialis), 2 i2 (dens incisivus lateralis), 3 c (dens caninus), 4 premaxilla, 4* maxilla, 5 nasal septum, 6 nasal ducts/conchae, 7 oral cavity, 8 tongue, 9 vomer, arrowhead organon vomeronasale/Jacobson’s organ. Dotted line sutura incisiva

From our results and studies of the literature we conclude that in the human the existence of the premaxilla can be regarded without doubt, the arguments are summarized in the following text.

The appearance of the premaxillary bone was reported by Mall (1906) as early as in a 16 mm human embryo; this is in line with our own observation. According to Fawcett (1911) ossification begins in a 17 mm embryo. Chase (1942) found the premaxilla in all embryos longer than 21.5 mm at first in 19 mm as a separate bone with a tendency of the premaxilla to appear later then the maxilla. He also stated that both bones had fused before the 25 mm stage. Concerning the palatine process he summarized that it normally grows directly from the body but may be separated in same cases. This also holds true for the Stenonian process.

Shepherd and McCarthy (1955), investigating fifteen human embryos, came generally to similar results like Jarmer (1922) who found a separate palatine process that soon fuses with the body. In the latter case the palatine process was not fully isolated, but thin-bony bridges connected it with the premaxillary corpus. Therefore the decision whether three isolated centers exist is a problem which is not conclusively resolved. Kölliker Th. (1882) vehemently argued for only one ossification center, although he only presented a few young embryos treated in caustic lye. Drawings from the bone visualized in such a manner are not very detailed. Histological sections from these filigree-like structures are absent and 30 to 50 μm-thick serial sections are shown from a 68 mm embryo only.

The authors who favor three ossification centers of premaxilla (Jarmer 1922, Peter 1924, Shepherd and McCarthy 1955) did not find totally isolated elements but rather fine trabeculae connections which show their belonging to the premaxilla. This is also the case in our material. Further evidence pointing toward separate anlagen is the persistence of the sutures. Beside the sutura incisiva between the palatine part of premaxilla and maxilla, a sutura intraincisiva separates the processus Stenonianus from the palatine process. Thus, we conclude that ossification of the premaxilla starts from three anlagen rather than to spread out from one center. However, we are of the same opinion as Peter (1924): “der morphologische Wert eines Skelettstücks wird also nicht durch die Zahl seiner Ossificationszentren gegeben, und damit verliert die Frage nach der Zahl der Anlagen der Intermaxillare ganz bedeutend an Wichtigkeit.”

While the number of more or less separated parts of the premaxilla is discussed, in recent times even the opinion that no separate ossification center of the premaxilla exists has found recent support. Wood et al. (1967) studied histological sections from embryos of the Carnegie Collection and were unable to find separate centers. Vacher et al. (1999, 2001a, 2001b), likewise, favor a single zone of ossification, in their opinion, it only persists a transverse mesenchymal septum as a “souvenir of an ancestral premaxilla.” In 1921, Macklin failed to note the very recognizable premaxilla with the sutura incisiva to the adjacent part of the maxilla in his famous reconstruction of the skull of a human fetus which was 43 mm at its greatest length. Müller and O’Rahilly (1979), in their detailed study on the skull of a stage 23 embryo do not mention the premaxilla. However, Kadanoff et al. (1970) found in 11.1% of palates in adults a sutura incisiva or remnants of it.

Despite its short individual existence, the existence of an individual premaxillary bone might be proved by an isolated agenesis of this bone. Fischel (1905) described the skull of a woman lacking the incisive teeth as well as crista nasalis and spina nasalis, a part of the upper jaw that clearly belongs to the premaxilla. Here the canines are the most medial teeth.

Another argument is the evolutionary aspect, Maurielle and Bar (1999) suggested a longer independence of some parts of the premaxilla in very young Neandertal children at the nasal aspect traces of the premaxillary suture. Yet, Neandertals are considered not to be a common ancestor to modern humans (Krings et al. 1997).

Finally, the phylogenetic aspect has to be taken into account as discussed by many authors since the time of Goethe as mentioned above.

Part II

The architecture of the premaxilla

The architecture of the premaxillary bone can be well understood by studying its development to an important three-dimensional structure in the mid-face region. The progressive growth of the facial processes from maxilla and premaxilla is demonstrated semi-schematically in Figure 9. The intermaxillary bone forms the main boundary of the apertura piriformis. In the elaborate reconstruction of Felber (1919), taken from a fetus in the fifth month (Fig. 9a), the frontal process of the premaxilla is seen in contact with the nasal bone which both form the osseous contour of the outer nasal aperture. In the adult (Fig. 9b), this part of premaxilla extends to the frontal bone and forms a wedge between maxilla and nasal bone. A schematic drawing (Fig. 9c) demonstrates the increasing growth of the frontal processes of maxilla and premaxilla towards the os frontale. At the facial plane, the sutura incisiva is bridged by osseous tissue caudally, while rostrally, a broad space still demarcates maxilla and premaxilla. The facial skull of a 7 month-old fetus only shows remnants of this part of the sutura incisiva (Fig. 9d). In adults, this line normally has disappeared. Therefore, most atlantes of anatomy do not show or even mention the important facial process of the premaxillary bone e.g., Putz and Pabst (2000). Ashley-Montagu (1936) studied about 10,000 crania of primates and humans. In the primates he founds in all cases the premaxilla and its suture lines visible on the facial aspect of the skull, whereas in humans all traces of the premaxilla on the facial aspect are obliterated as early as in the third fetal month. Yet he has observed portions of the premaxilla on the facial aspect in 7.2 percent of Negro fetuses and 1.6 per cent of white fetuses. Portions of this bone may occasionally be seen lateral to the apertura piriformis as late as the fifth year. Inferior to the apertura traces of the premaxilla are never present.
Fig. 9a–d

Reconstruction of the right bony upper jaw in a human fetus in the fifth month. a facial view, Bar 1 mm. b Position of the sutura incisiva at the facial side of the maxilla in adults (after Felber 1919). a, b, d: dark premaxilla, C canine, J1(i1) medial incisor, J2(i2) lateral incisor, M1 molar, M maxilla, F os frontale, N os nasale, V vomer, a.p. apertura piriformis, s.i. sutura incisiva, s.p. sutura palatina, sp.n spina nasalis (processus Stenonianus). 1 os frontale, 2 os nasale, 3 frontal process of premaxilla, 4 frontal process of maxilla, 5 maxilla, 6 premaxilla, 7 processus Stenonianus/crista nasalis with septum nasi, 8 projection of the sutura incisiva into the facial side of the adult maxilla, *-* remnants of the sutura incisiva frontalis, thin line projection of the former sutura incisiva on the facial plane. c Schematic drawing to demonstrate the progressive growth of the right facial processes from maxilla as well as premaxilla including the fusion line. 1 premaxilla, 2 maxilla, 3 processus frontalis premaxillaris, 4 processus frontalis maxillaris, 5 processus Stenonianus/spina nasalis, 6 apertura piriformis, i1 medial incisor, i2 lateral incisor, c canine, m molar, arrowheads former sutura incisiva, * sutura incisiva, long arrow direction of growth towards the os frontale. d Part (half-enface) of the right facial skull of a human fetus of the seventh month with 42 cm CHL. Bar 1 cm

The significance of this part of the face is well documented by Benninghoff’s trajectories of the skull, showing a strong line of stress named the frontonasal pillar (Benninghoff and Goerttler 1961) or nasal pillar (Toldt 1914, cited by Witzel and Preuschoft 2002). This was recently confirmed by the finite element analysis (Witzel 2002, Witzel and Preuschoft 2002). According to these authors “the lateral walls of the nasal cavity are the most highly stressed pillars that connect the upper jaw with the braincase, particular at both sides of the apertura piriformis.” Similarly, Lautrou (2002) shows a “centromaxillaire” bordering the capsule nasal.

The premaxilla development in relation to the movement of the nasal septum

The intercalation of the trapezoid alveolar part of the premaxilla into the maxillary arch and its contact with the inferior part of the developing nasal septum plays an essential role during palate closure (Figs. 10, 11). As can be seen in Figure 10a, the nasal septum anlage arises in direct neighborhood to the anlage of the intermaxillary bone. Simultaneously with the closure of primary and secondary palate, it grows dorsally. In a dorsal view (Fig. 10b) the nasal septum appears carinated moving backward, while the palatine halves grow medially. The direction of septum elongation is indicated in Figure 10c. Likewise the facial vertical growth is indicated (for functional analysis see Moss 1964, 1968). Thus, the premaxilla acts as a stabilizing element within the facial skeleton comparable with a keystone in a Roman arch (Fig. 10d). This is documented in Figure 11b showing the relation of palatine closure and nasal septum as it happens in a stage 22 or stage 23 embryo. The situation in a stage 19 embryo is represented in the partial reconstruction (Fig. 11a) when the palatine bulges embrace the tongue. Thus during the formation of the primary mouth roof, the elevation of the palatine shelves has to be taken into consideration.
Fig. 10a–d

Schematic drawings to demonstrate the intercalation of the trapezoid os premaxillare into the maxillary arch and into the nasal septum during palatine closure (a, b, c). The premaxilla acts as a vertical stabilizing element within the facial skull (c) and is comparable to the keystone within a Roman arch (d). a curved arrows direction of the fusing palatine shelves towards medial, short arrows growth direction of the nasal septum towards dorsal. b Dorsal view of a, note the carinate nasal septum. c Big arrow forces acting vertically on the premaxilla as well as direction of growth towards cranial, small arrow direction of growth of the nasal septum. d Roman arch with keystone. 1 os premaxillare, 2 palatine shelves, 3 bulge of upper jaw/alveolar ridge, 4 apertura piriformis, 5 nasal septum, 6 keystone, 7 Roman arch

Fig. 11 a

Partial reconstruction of the head of a stage 19 embryo, 17.5 mm GL, seventh week, frontal sectioned, semi-thin. Dorsal view (section) to the right and rostral. Palatine shelves embrace the tongue at this level. Note the prolongation of the nasal septum from rostral to dorsal. 1 nasal septum, 2 tongue, 3 palatine shelves, 4 Meckel’s cartilage, 5 eye, 6 crista galli, 7 cartilaginous nose, 8 external ear anlage, * nasal ducts, arrowheads slice dental anlage of upper and lower jaw. b Schematic drawing to demonstrate the relations of palatine closure and growth of nasal septum related to an embryo of 26/28 mm GL, lingual view. The intercalated premaxilla within the rostral basis of the nasal septum: punctuated. 1 nasal septum, 2 palatine shelves, 3 uvula

The central position of the septum nasi within the face is also evident in a stage 23 embryo. In Figure 12a three sagittal blocks combined in a step-like manner to demonstrate the anterior position of the septum nasi that rest upon the anterior part of the fused palate. The vomeronasal (Jacobson’s) organ has formed within the nasal septum. Dorsally, the free border of one palatine shelf is shown to line the nasopharyngeal space.
Fig. 12 a

Graphic reconstruction of block sections of the right half of the head of a stage 23-embryo, 29 mm GL, 10 μm. Three blocks are moved apart to frontal views. b Reconstruction block of the same embryo as in a. View from dorsal to ventral into oral cavity and nasopharynx, tongue not shown. 1 eye, 2 epithelial nasal plug, 3 cartilaginous outer nasal wall, 4 nasal duct, 5 nasal septum with Jacobson’s organ in a, 6 cartilaginous base of skull, 7 anlagen of adeno- and neurohypophysis, 8 nasopharynx, 9 orifice of tuba auditiva, 10 section of the already fused palatine shelves, 11 free border of the right palatine shelf, thus, not fused, 12 tongue, 13 Meckel’s cartilage, 14 lower lip, 15 oral cavity, * fused palate, arrow fusion line of palate and nasal septum. Footnote: the reconstructions shown in Figures 12a, b (this manuscript), as well as the Figures 23 to 27a, b and 23 to 28a, b in Hinrichsen KV (1990) ed.: Humanembryologie, Springer Berlin Heidelberg, were subject of two posters (not to be cited). (1) Hinrichsen KV, Jacob HJ, Barteczko KJ (1985) Weitere Befunde zur frühen Gesichtsentwicklung des Menschen. Sixth scientific conference of the GfE (Society of Developmental Biology) in association with the Nederlandse Vereniging voor Ontwikklingsbiologie, Bochum. (2) Hinrichsen KV, Barteczko KJ (1986) Gaumenbildung und Nasenseptum bei menschlichen Embryonen. 36th conference of the German Society of Maxillofacial Surgery, Bochum. According to these results K Barteczko has been touched up the models to the development of face by Peter (1911) of stage 15, 6.0 mm, stage 17–10.3 mm, stage 18–16.5 mm, stage 23–28 mm, traded by SOMSO, Coburg (see also Fig. 12) as has been demonstrated in poster 1

A reconstruction block with a dorso-ventral view (Fig. 12b) proofs the keel-shaped nasal septum not to come from the base of the skull, but arises ventrally and grows backwards synchronously with the palatine shelves closure. Thus, the point of contact between nasal septum and palatine is an essential hallmark.

The final relation of the premaxilla to the septum nasi is reported in detail by Mosher (1909) and Klaff (1956): at birth, two structures of the premaxilla, the anterior nasal spine and the premaxillary wings become component parts of the nasal septum. The premaxillary wings project obliquely upward and fuse with the tip of the vomer at 15 years of age. According to Mosher (1909) “the tip of the vomer rest in the gutter of the premaxillary wings, and the tip of the premaxillary wings rests in the gutter of the nasal spines, like the arrangement of the sections of the old-fashioned V-shaped wooden drain.”

Synopsis of palatine closure

The significance of the premaxillary bone anlage for the closure of the palatine has already been mentioned. Here, we represent a synopsis of the phases of this process starting with a stage 16 embryo, 10.2 mm GL (Fig. 13a) up to a 49 mm-fetus GL about 10 weeks (Fig. 13x). The soft tissue, into the palatine process of the premaxilla develops, is the primary palate. It originates from the globular process of the medial nasal swelling, which fuses superficially with the maxillary process that generates the secondary palate shelves. Palatine closure is initiated by the fusion of the paired primary palate. The secondary palatine shelves grow medially with their anterior border, always in close relation to the posterior edge of the primary palate. This demarcation coincides with the sutura incisiva. The closure of the secondary palate starts at the foramen incisivum in dorsal direction. According to Luke (1976), in the 30 mm-embryo, the palatal shelves are elevated above the tongue and approach to the nasal septum (Peter 1924), and this may be due to active tongue movement (Inouye 1912, cited by Braus and Elze 1934); or other factors such as the diminution of the angulus occipitalis due to the increasing brain volume, or the increasing size of the arcus mandibulae (Aronov 1972).
Fig. 13a–x

Graphic synopsis of palate closure from a 10.2 mm GL embryo. a. A fetus of 49 mm GL. x. Under consideration of the premaxilla, lingual view (out of scale!)

Thus palatal closure is not only the fusion of the palatal shelves but a soldering of three structures as already described. The palatine processes and the nasal septum start to fuse at stage 23. Complete fusion seems to be incomplete until the 12th week (Yoon et al. 2000). SEM images of Waterman (1974) demonstrated alterations of surface epithelium associated with cell death during the fusion process in humans.

In our last stage (49 mm), bone forms within the secondary palate. Only isolated epithelial nests remind the palatal fusion superficial (Luke 1976). Structure and glycogen content in this epithelial seam was studied by Meller and Barton (1979).

Fusion and elevation of the palatal shelves, at least in mice, is combined with the accumulation of glycosaminoglycans (Knudsen et al. 1985). Especially, the expression of chondroitin sulfate proteoglycan on the apical surface of the seam epithelial is important in palatal shelf adhesion and is supposed to be regulated by TGF-b3 (Gato et al. 2002) while BMP and Shh signals seem to regulate the growth of the anterior region of palate (Zhang et al. 2002). Recently, the role of the transcription factor Tbx22 in palatogenesis was discussed (Bush et al. 2003; Herr et al. 2003). Expression is found in the inferior nasal septum and the palatal shelf before fusion.

Part III

The premaxilla in relation to the development of the human face

The prenatal development of the human face is characterized by the heads extension and the simultaneous outgrowth of the midfacial region. This process can be demonstrated by a line connecting Rathke’s pouch (hypophysis) and nasal grooves in embryos from 10 to 39 mm GL (Fig. 14). All embryos are drawn with the same scale. In Figure 15, a superposition of all embryos clearly shows not only an enormous increase of length of this diameter, but also an increase in the angle between this line and the body axis.
Fig. 14a–d

The outgrowth of the human face with simultaneous extension of the head demonstrated with the aid of a line combining hypophysis and outer nose in embryos of: a 10 mm; b 17.5 mm; c 26 mm; d 39 mm. All with identical scale, bar 1 mm. 1 hypophysis/Rathke’s pouch, 2 nasal pit/extremitas nasalis, 3 tongue, 4 palate, 5 anlage of nasal septum

Fig. 15

All four embryos projected over each other near hypophysis as reference point. Bar 1 mm

Disturbance of the facial outgrowth may cause protrusion, closed bite or prognathism. Since facial structures develop from the facial processes which consist of neural crest derived mesenchyme (Noden 1984, 1988), defects in the signaling interactions of epithelium and mesenchyme, as reviewed by Francis-West et al. (1998) and Francis-West et al. (2003) might cause such malformations and Msx-1 and Pax 6 seem to be involved in premaxillary development.

In the later fetal and postnatal period facial outgrowth is due to bone growth and the growth pattern of sutures (see for references Meikle 2002), perhaps under the influence of TGF-b (Adab et al. 2002).

Rudimentary premaxillary bones are generally found to be combined with other defects. In fetuses with holoprosencephaly, the premaxilla was often absent or reduced (Arnold et al. 1998b; Kjaer et al. 1997). Etiological factors affected with these malformations are supposed to act at an early embryological stage (Sedano 1970) like disturbance of the mesoderm anterior to the notochord (Kjaer et al. 1997). Data on experimentally-induced holoprosencephaly in the golden hamster even suggest that alterations in selected proteins in the prechordal mesoderm and adjacent floor plate, impair the adjacent neural plate and neural crest and, thus, induce these anomalies (Coventry et al. 1998). Similarly, the anticancer agent suramin was found to cause midfacial defects in chicken (Männer et al. 2003).

The relation of premaxillary development and lip/palate clefts

We do not wish to focus on the development of lip/palate clefts, but some remarks should be mentioned. The position of the lateral clefts is not always identical with the course of the sutura incisiva, which demarks the bony part of the premaxilla (Delaire 1965). An example for this fact gives the double formation of the upper–lateral incisor as shown in an adult (Fig. 16a) and a 55-mm fetus (Fig. 16b). Obviously the cleft divides the alveolar anlage of this tooth. As referred to by Grünberg (1960), palate clefts often coincide with supernumerary incisors, and Warynski (1888) even believed that in all cases of lateral palatine clefts such a phenomenon may be observed (Inouye 1912). Experiments of Wei et al. (2002) on normal and cleft lip/palate monkeys argue that the ossification of the premaxilla spreads laterally across the medial nasal process and the maxillary process fusion line (see above). The lateral incisor, which has formed within the maxillary process, undergoes a complex positional shift, related to the sutura incisiva and is finally located medial to it. According to Lisson and Kjaer (1997) the incisive fissure is not the location of clefts, but clefting occurs at the fusion line between medial nasal process and maxillary process, which runs to the lateral incisor. Thus, supernumerary lateral incisors may be regarded as a minor form of clefting. Arnold et al. (1998a), studying epithelial pearl and tooth buds in human fetuses with cleft lip and palate, argue that a post-fusion phenomenon in these anomalies is likely, and that a secondary rupture of the premaxilla would affect the dental lamina and result in missing teeth or duplication of tooth buds. However, the mechanism of such a phenomenon is not clearly understood.
Fig. 16

Double anlage of the lateral upper incisor, left side (asterisk with 3) in a. (With kind permission of Prof. Dr. Dr. K-D. Wolff, head of the Mouth, Jaw and Plastic Surgery Department, Knappschaftskrankenhaus, Ruhr-University Bochum, Germany). b Transversal section of a 55-mm fetus (the same fetus as in Fig. 7g, h) with a double anlage of the lateral–upper incisor, right side. Magnification: b ×20. 1 alveolar part of the premaxilla, 5 incisive suture, 12 sutura palatina mediana, 13 N. nasopalatinus in the incisive foramen, i1 dens incisivus medialis, i2 dens incisivus lateralis, i3 dens incisivus lateralis secundus, * sutura intraincisiva

According to the morphogenetic classification of craniofacial anomalies by Pfeifer (1986), Gundlach and Pfeifer (1981), defects or aplasia of the premaxilla belong to the prosencephalic anomalies. In the area between the forehead and the lateral/back region of the head, which is a more passive zone during development, most malformations of the head are found with lip palate clefts being predominant. These are caused by multifactorial variations.

Mooney et al. (1991) suggest growth deficits from 14 to 21 weeks causing clefts rather than reduced mesenchymal ingrowth into the nasal fin at an earlier stage as proposed by Diewert and Shiota (1990) who found a reduced thickness. Thus the role of BMPs that regulate proliferation and patterning of facial mesenchyme has been studied by Ashique et al. (2002). Similarly, Tgf-betas and Msx2 are suggested as having a role in active postnatal facial growth (Adab et al. 2002). Furthermore, the role of epithelium in the pathogenesis of cleft lip and palates was pointed out by Millicovsky and Johnston (1981) and Millicovsky et al. (1982), although a combination of genetic and environmental factors may cause these defects.


Describing the existence, development and impact of the premaxillary bone during the facial development in humans, we have arrived at the following conclusions.

1. Goethe (1784) was not the first discoverer of this bone in humans. Prior to him, Coiter (1573), Broussonet (1779) and finally Vicq d’Azyr (1780) observed and/or described this structure in the human. The conclusive literature to this topic is discussed.

2. At the end of the nineteenth and early twentieth century, a dispute arose between the great anatomists concerning parts of the anlage of premaxilla and consequently the number of ossification centers, as well as the position of the incisive suture and the existence of other suturae e.g., sutura intraincisiva, sutura intraalveolaris. This is not the topic today, but again there are scientists who are against the original development of the intermaxillary bone. To demonstrate early stages of premaxillary development we used reconstructions of the nearly forgotten embryologists Felber 1919, and Jarmer 1922, and our own serial sections of embryos from 16 mm to 68 mm. We are convinced by these observations that an original premaxilla exists. Its ossification was first observed in a 16 mm embryo. We are favoring three pairs of anlagen which are not completely separate centers but connected by thin bony lamellae: (1) the alveolar part including the facial process, (2) the palatine part, and (3) the processus Stenonianus. Prevail sutura incisiva and a shorter sutura intraincisiva argue in this sense. Fusion of the premaxillary and maxillary bones is nearly complete in the fifth month. Parts of the palatine as well the facial part of the incisive suture may rarely persist. In a 42 cm CHL (Crown-Heel Length) prematurely born child, a short section of its facial part is still visible.

3. The premaxilla is considered to be very important stabilizing element of the facial skull. Together with the ossa nasales it encloses the apertura piriformis and punctually contacts the ossa frontales. It contains the upper incisors. Together with the maxillary bones, it fulfils an important supporting function in biting and mastication. A vertical bony pillar connecting the basis of the skull dorsocranially consists of the premaxilla (crista nasalis) and the intercalated vomer. The comparison with the keystone in a Roman arch, the removal of this would cause the collapse of the suggested arch itself.

4. The mesenchymal anlage of the premaxilla as primary palate plays an important role in the palatinal closure and therefore the separation of the oral cavity from the pharynx and the two nasal ducts. The palatinal anlagen of the premaxilla are the pioneers in the fusion process, followed by closure of the secondary palatine. Simultaneously, the nasal septum, intercalated caudally with the premaxilla, grows dorsad to contact the basis of the skull and thus separates the nasopharyngeal space. Interestingly, the growth of the nasal septum always delays the fusion of the palatine a little. In a synopsis this process of closure is documented in embryos from 10.2 mm to 49 mm GL.

5. The formation of the human face is characterized by the simultaneous extension of the head and the outgrowth of the facial skull. A measuring line between hypophysis and nasal pit compared in embryos from 10 mm to 39 mm GL helps to make this process visible. An abnormal outgrowth may cause protrusion, closed bite or prognathism.

6. It was not the aim of this paper to focus on the development of cleft lip and palate. Although we wish to make some comments: the position of the clefts is not always identical with that of the incisive suture, demarcating the bony premaxilla. An example is given by the double anlage of an upper outer incisor in a 55-mm fetus and an adult. Cleft lip and palate are supposed to have a multifactorial etiology. They may occur very early within the epithelial–mesenchymal anlage or later after the fusion of facial processes with possible duplication of the lateral–upper incisor


We particularly thank Dr. med. Sigurd Große-Oetringhaus (Dortmund) for reading the manuscript and Dr. med. Heinz Jürgen Jacob who kindly provided the SEM in Figure 4 c, d and e. We are grateful to Mrs. Annegrit Schlichting for technical assistance, Mrs. Antje Jaeger and Mrs. Marion Otto for expert photographic work.

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