Abstract
Writing a chapter on the embryology of occult spinal dysraphic malformations (OSDM) is a little like writing a historical fiction novel. We begin with a substantial knowledge about the cellular events, molecular biology, and biomechanics underlying normal avian and mammalian neural development – knowledge derived from a host of embryonic experimental manipulations and genetic mutations. From this we propose, largely by extension, a paradigm for normal human neural development that comports with our clinical observations and theorize about the embryogenesis of human neural tube defects (NTD) of myelomeningocele and exencephaly/anencephaly, for which we have reasonable experimental models. We are finally left to essentially fantasize about the embryogenesis of OSDM, for which we have virtually no animal models or experimental data. Many of the theories we will discuss in this chapter were created de novo decades ago from clinical observations and a basic understanding of morphogenesis, unmodified by subsequent advances in cellular and molecular biology. It is our hope that the future will bring greater clarity to our understanding about the embryogenesis of these malformations. Until then, a work of fiction will have to suffice.
We begin this chapter with an update about what is known about normal human embryogenesis and our present understanding about NTDs and then review present theories about the embryogenesis of various OSDM.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
O’Rahilly R, Müller F. Developmental stages in human embryos. Washington, DC: Carnegie Institution of Washington; 1987.
Jellinger K, Gross H, Kaltenbäch E, Griswold W. Holoprosencephaly and agenesis of the corpus callosum: frequency of associated malformations. Acta Neuropathol. 1981;55:1–10.
Vakaet L. Some new data concerning the formation of the definitive endoblast in the chick embryo. J Embryol Exp Morpholog. 1962;10:38–57.
Modak SP. Experimental analysis of the origin of the embryonic endoblast in birds. Rev Suisse Zool. 1966;73:877–908.
Fontaine J, Le Douarin NM. Analysis of endoderm formation in the avian blastoderm by the use of quail-chick chimaeras. The problem of the neurectodermal origin of the cells of the APUD system. J Embryol Exp Morpholog. 1977;41:209–22.
Rosenquist GC. A radioautographic study of labeled grafts in the chick blastoderm. Development from primitive streak stages to stage 12. Contrib Embryol. 1966;38(262):73–110.
Nicolet. Analyse autoradiographique de la localisation des différentes ébauches présomptives dans la ligne primitive de l’embryon de Poulet. J Embryol Exp Morpholog. 1970;23:79–108.
Nicolet G. Avian gastrulation. Adv Morph. 1971;9:231–62.
Shaw W. Observations on two specimens of early human ova. Brit Med J. 1932;1:411–5.
O’Rahilly R, Müller F. The first appearance of the human nervous system at stage 8. Anat Embryol. 1981;163:1–13.
Müller F, O’Rahilly R. The development of the human brain and the closure of the rostral neuropore at stage 11. Anat Embryol. 1986;175:205–22.
Müller F, O’Rahilly R. The first appearance of the neural tube and optic primordium in the human embryo at stage 10. Anat Embryol. 1985;172:157–69.
Müller F, O’Rahilly R. The development of the human brain, the closure of the caudal neuropore, and the beginning of secondary neurulation at stage 12. Anat Embryol. 1987;176:413–30.
O’Rahilly R. Developmental stages in human embryos, including a survey of the Carnegie collection. Part A: embryos of the first three weeks (stages 1 to 9), Carnegie Institution of Washington publication no. 631. Washington, DC: Carnegie Institution of Washington; 1973.
Müller F, O’Rahilly R. The first appearance of the major subdivisions of the human brain at stage 9. Anat Embryol. 1983;168:419–32.
Golden JA, Chernoff GF. Multiple sites of anterior neural tube closure in humans: evidence from anterior neural tube defects (anencephaly). Pediatrics. 1995;95:506–10.
Golden JA, Chernoff GF. Intermittent pattern of neural tube closure in two strains of mice. Teratology. 1993;47:73–80.
Van Allen MI, Kalousek DK, Chernoff GF, Juriloff D, Harris M, McGillivray BC, et al. Evidence for multi-site closure of the neural tube in humans. Am J Med Genet. 1993;47:723–43.
Copp AJ, Greene NDE. Genetics and development of neural tube defects. J Pathol. 2010;220:217–30.
Müller F, O’Rahilly R. Cerebral dysraphia (future anencephaly) in a human twin embryo at stage 13. Teratology. 1984;30:167–77.
Urioste M, Rosa A. Anencephaly and faciocranioschisis: evidence of complete failure of closure 3 of the neural tube in humans. Am J Med Genet. 1998;75:4–6.
NIkolopoulou E, Galea GL, Rolo A, Greene NDE, Copp AJ. Neural tube closure: cellular, molecular and biomechanical mechanisms. Development. 2017;144:552–66.
Schoenwolf GC. Shaping and bending of the avian neuroepithelium: morphometric analyses. Dev Biol. 1985;109:127–39.
Nicolopoulos-Stournaras S, Iles JF. Motor neuron columns in the lumbar spinal cord of the rat. J Comp Neurol. 1983;217:75–85.
Schoenwolf GC, Smith JL. Mechanisms of neurulation: traditional viewpoint and recent advances. Development. 1990;109:243–70.
Smith JL, Schoenwolf GC. Notochordal induction of cell wedging in the chick neural plate and its role in neural tube formation. J Exp Zool. 1989;250:49–62.
van Straaten HWM, Hekking JWM, Wiertz-Hoessels EJLM, Thors F, Drukker J. Effect of the notochord on the differentiation of a floor plate area in the neural tube of the chick embryo. Anat Embryol. 1988;177:317–24.
Hammerschmidt M, Brook A, McMahon AP. The world according to hedgehog. Trends Genet. 1997;13:14–21.
Rifat Y, Parekh V, Wilanowski T, Hislop NR, Auden A, Ting SB, et al. Regional neural tube closure defined by the Grainy head-like transcription factors. Dev Biol. 2010;345:237–45.
George TM, McLone DG. Mechanisms of mutant genes in spina bifida: a review of implications from animal models. Pediatr Neurosurg. 1996;23:236–45.
Chatkupt S, Johnson WG. Waardenburg syndrome and myelomeningocele in a family. J Med Genet. 1993;30:83–4.
Agopian AJ, Bhalla AD, Boerwinkle E, Finnell RH, Grove ML, Hixson JE, et al. Exon sequencing of PAX3 and T (brachyury) in cases with spina bifida. Birth Defects Res A Clin Mol Teratol. 2013;97:597–601.
Zhao T, Gan Q, Stokes A, Lassiter RNT, Wang Y, Chan J, et al. β-catenin regulates Pax3 and Cdx2 for caudal neural tube closure and elongation. Development. 2014;141:148–57.
Schoenwolf GC. Tail (end) bud contributions to the posterior region of the chick embryo. J Exp Zool. 1977;201:227–46.
Schoenwolf GC, DeLongo J. Ultrastructure of secondary neurulation in the chick embryo. Am J Anat. 1980;158:43–63.
Schoenwolf GC. Histological and ultrastructural studies of secondary neurulation in mouse embryos. Am J Anat. 1984;169:361–76.
Lemire RJ. Secondary caudal neural tube formation. In: Lemire RJ, Loeser JD, Leech RW, Ellsworth Jr CA, editors. Normal and abnormal development of the human nervous system. Hagerstown: Harper and Row; 1975. p. 71–83.
Bolli P. Sekundäre Lumenbildungen im Neuralrohr und Rückenmark menschlicher Embryonen. Acta Anat. 1966;64:48–81.
Yang HJ, Lee DH, Lee YJ, Chi JG, Lee JY, Phi JH, et al. Secondary neurulation of human embryos: morphological changes and the expression of neuronal antigens. Childs Nerv Syst. 2014;30:73–82.
Yang HJ, Wang KC, Chi JG, Lee MS, Lee YJ, Kim SK, et al. Neural differentiation of caudal cell mass (secondary neurulation) in chick embryos: Hamburger and Hamilton stages 16–45. Dev Brain Res. 2003;142:31–6.
Chung YN, Lee DH, Yang HJ, Kim SK, Lee YJ, Lee MS, et al. Expression of neuronal markers in the secondary neurulation of chick embryos. Childs Nerv Syst. 2008;24:105–10.
Beck CW. Development of the vertebrate tailbud. WIREs Dev Biol. 2015;4:33–44.
van de Ven C, Bialecka M, Neijts R, Young T, Rowland JE, Stringer EJ, et al. Concerted involvement of Cdx/Hox genes and Wnt signaling in morphogenesis of the caudal neural tube and cloacal derivatives from the posterior growth zone. Development. 2011;138:3451–62.
Dady A, Havis E, Escriou V, Catala M, Duband J-L. Junctional neurulation: a unique developmental program shaping a discrete region of the spinal cord highly susceptible to neural tube defects. J Neurosci. 2014;34:13208–21.
Eibach S, Moes GS, Hou YJ, Zovickian J, Pang D. Unjoined primary and secondary neural tubes: junctional neural tube defect, a new form of spinal dysraphism caused by disturbance of junctional neurulation. Childs Nerv Syst. 2017;33:1633–47.
Streeter GL. Factors involved in the formation of the filum terminale. Am J Anat. 1919;25:1–11.
Kunimoto K. The development and reduction of the tail and of the caudal end of the spinal cord. Contrib Embryol. 1918;8:161–98.
DiPietro MA. The conus medullaris: normal US findings throughout childhood. Radiology. 1993;188:149–53.
Wilson DA, Prince JR. MR imaging determination of the location of the normal conus medullaris throughout childhood. Am J Radiol. 1989;152:1029–32.
Wolfe S, Schneble F, Tröger J. The conus medullaris: time of ascendance to normal level. Pediatr Radiol. 1992;22:590–2.
Barson AJ. The vertebral level of termination of the spinal cord during normal and abnormal development. J Anat. 1970;106:489–97.
James CCM, Lassman LP. Spinal dysraphism. Spina bifida occulta. London: Butterworths; 1972.. 144 p
Barson AJ. Spina bifida: the significance of the level and extent of the defect to the morphogenesis. Dev Med Child Neurol. 1970;12:129–44.
Kesler H, Dias MS, Kalapos P. The normal position of the conus medullaris in children: a whole-spine MRI study. Neurosurg Focus. 2007;23(2):1–5.
Copp AJ, Greene NDE. Neural tube defects – disorders of neurulation and related embryonic processes. Wiley Interdiscip Rev Dev Biol. 2013;2:213–27.
Ackerman LL, Menezes AH. Spinal congenital dermal sinuses: a 30-year experience. Pediatrics. 2003;112:641–7.
Pang D, Zovickian J, Wong ST, Hou YJ, Moes GS. Limited dorsal myeloschisis: a not-so-rare form of primary neurulation defect. Childs Nerv Syst. 2013;29:1459–84.
de Vloo P, Lagae L, Sciot R, Demaerel P, van Loon J, van Calenbergh F. Spinal dermal sinuses and dermal sinus-like stalks analysis of 14 cases with suggestions for embryologic mechanisms resulting in dermal sinus-like stalks. Eur J Paediatr Neurol. 2013;17:575–84.
Eibach S, Moes GS, Zovickian J, Pang D. Limited dorsal myeloschisis associated with dermoid elements. Childs Nerv Syst. 2016;33:55–67.
Dias MS, Partington MD. Congenital brain and spinal cord malformations and their associated cutaneous markers. Pediatrics. 2015;136:1105–19.
Weprin BE, Oakes WJ. Coccygeal pits. Pediatrics. 2005;105:e69–73.
Walker AE, Bucy PC. Congenital dermal sinuses; a source of spinal meningeal infection and subdural abscesses. Brain. 1934;57:401–21.
Pang D, Dias MS. Cervical myelomeningoceles. Neurosurgery. 1993;33:363–73.
Aaronson I. Anterior sacral meningocele, anal canal duplication cyst and covered anus occurring in one family. J Pediatr Surg. 1970;5:559–63.
Steinbok P. Dysraphic lesions of the cervical spinal cord. Neurosurg Clin N Am. 1985;6:367–76.
Steinbok P, Cochrane DD. The nature of congenital posterior cervical or cervicothoracic midline cutaneous mass lesions. Report of eight cases. J Neurosurg. 1991;75:206–12.
Ehni G, Love JG. Intraspinal lipomas: report of cases, review of the literature, and clinical and pathologic study. Arch Neurol Psychiatr. 1945;53:1–28.
Lassman LP, James CCM. Lumbosacral lipomas: critical survey of 26 cases submitted to laminectomy. J Neurol Neurosurg Psychiatry. 1967;30:174–81.
McLone DG, Mutluer S, Naidich TP. Lipomeningoceles of the conus medullaris. In: Raimondi AJ, editor. Concepts in pediatric neurosurgery. 3rd ed. Basel: S. Karger; 1983. p. 170–7.
Walsh JW, Markesbery WR. Histological features of congenital lipomas of the lower spinal canal. J Neurosurg. 1980;52:564–9.
Chapman PH. Congenital intraspinal lipomas: anatomical considerations and surgical treatment. Childs Brain. 1982;9:37–47.
Pang D. Long-term outcome of total and near-total resection of spinal cord lipomas and radical reconstruction of the neural placode: part I – surgical technique. Neurosurgery. 2009;65:511–29.
Morota N, Ihara S, Ogiwara H. New classification of spinal lipomas based on embryonic stage. J Neurosurg Pediatr. 2017;19:428–39.
Naidich TP, McLone DG, Mutluer S. A new understanding of dorsal dysraphism with lipoma (lipomyeloschisis): radiologic evaluation and surgical correction. Am J Roentgenol. 1983;140:1065–78.
McLone DG, Naidich TP. Spinal dysraphism: experimental and clinical. In: Holtzman RN, Stein BM, editors. The tethered spinal cord. New York: Thieme-Stratton; 1985. p. 14–28.
French BN. Abnormal development of the central nervous system. In: McLaurin RL, Venes JL, Schut L, Epstein F, editors. Pediatric neurosurgery: surgery of the developing nervous system. 2nd ed. Philadelphia: W.B. Saunders Co.; 1989. p. 9–34.
George TM, Adamson DC. Normal and abnormal development of the nervous system. In: Albright AL, Pollack IF, Adelson PD, editors. Principles and practice of pediatric neurosurgery. New York: Thieme; 2015. p. 10–26.
Bentley JFR, Smith JR. Developmental posterior enteric remnants and spinal malformations. The split notochord syndrome. Am J Dis Child. 1960;35:76–86.
Prop N, Frensdorf EL, van de Stadt FR. A postvertebral entodermal cyst associated with axial deformities: a case showing the “entodermal-ectodermal adhesion syndrome”. Pediatrics. 1967;39:555–62.
Bremer JL. Dorsal intestinal fistula; accessory neurenteric canal; diastematomyelia. Arch Pathol. 1952;54:132–8.
Cohen J, Sledge CB. Diastematomyelia. An embryological interpretation with report of a case. Am J Dis Child. 1960;100:127–33.
Herren RY, Edwards JE. Diplomyelia (duplication of the spinal cord). Arch Pathol. 1940;30:1203–14.
Naidich TP, Harwood-Nash DC. Diastematomyelia: hemicord and meningeal sheaths; single and double arachnoid and dural tubes. Am J Neuroradiol. 1983;4:633–6.
James CCM, Lassman JP. Diastematomyelia. A critical survey of 24 cases submitted to laminectomy. Arch Dis Child. 1964;39:125–30.
Pang D. Split cord malformation: part II: the clinical syndrome. Neurosurgery. 1992;31:481–500.
Pang D. Tethered cord syndrome. Neurosurgery: state of the art reviews. 1st ed. Philadelphia: Hanley and Belfus; 1986. p. 45–79.
Ross GW, Swanson SA, Perentes E, Urich H. Ectopic midline spinal ganglion in diastematomyelia: a study of its connections. J Neurol Neurosurg Psychiatry. 1988;51:1231–4.
Lichtenstein BW. “Spinal dysraphism”. Spina bifida and myelodysplasia. Arch Neurol. 1940;44:792–810.
Rokos J. Pathogenesis of diastematomyelia and spina bifida. J Pathol. 1975;117:155–61.
Dias MS, Walker ML. The embryogenesis of complex dysraphic malformations: a disorder of gastrulation? Pediatr Neurosurg. 1992;18:229–53.
Gardner WJ. The dysraphic states from syringomyelia to anencephaly. Amsterdam: Excerpta Medica; 1973.. 201 p
Beardmore HE, Wigglesworth FW. Vertebral anomalies and alimentary duplications. Pediatr Clin N Am. 1958;5:457–74.
Burrows FGO, Sutcliffe J. The split notochord syndrome. Br J Radiol. 1968;41:844–7.
McLetchie NGB, Purves JK, Saunders RL. The genesis of gastric and certain intestinal diverticula and enterogenous cysts. Surg Gynecol Obstet. 1954;99:135–41.
Saunders RL. Combined anterior and posterior spina bifida in a living neonatal human female. Anat Rec. 1943;87:255–78.
Dodds GS. Anterior and posterior rachischisis. Am J Pathol. 1941;17:861–72.
Feller A, Sternberg H. Zur Kenntnis der Fehlbildungen der Wirbelsäule. I. Die Wirbelkörperspalte und ihre formale Genese. Virchow Arch Pathol Anat. 1929;272:613–40.
Fernbach SK, Naidich TP, McLone DG, Leestma JE. Computed tomography of primary intrathecal Wilms tumor with diastematomyelia. J Comput Assist Tomogr. 1984;8:523–8.
Cameron AH. Malformations of the neuro-spinal axis, urogenital tract and foregut in spina bifida attributable to disturbances of the blastopore. J Path Bact. 1957;73:213–21.
Ugarte N, Gonzalez-Crussi F, Sotelo-Avila C. Diastematomyelia associated with teratoma. J Neurosurg. 1980;53:720–5.
Emura T, Asashima M, Furue M, Hashizume K. Experimental split cord malformations. Pediatr Neurosurg. 2002;36:229–35.
Emura T, Asashima M, Hashizume K. An experimental animal model of split cord malformation. Pediatr Neurosurg. 2000;33:283–92.
Müller F, O’Rahilly R. Somitic-vertebral correlation and vertebral levels in the human embryo. Am J Anat. 1986;177:3–19.
Peacock WJ, Murovic JA. Magnetic resonance imaging in myelocystoceles. Report of two cases. J Neurosurg. 1989;70:804–7.
McLone DG, Naidich TP. Terminal myelocystocele. Neurosurgery. 1985;16:36–43.
Carey JC, Greenbaum B, Hall BD. The OEIS complex (omphalocele, extrophy, imperforate anus, spinal defects). Birth Defects. 1978;14(6B):253–63.
Lemire RJ, Beckwith JB. Pathogenesis of congenital tumors and malformations of the sacrococcygeal region. Teratology. 1982;25:201–13.
Lee JY, Kim SP, Kim SW, Park S-H, Choi JW, Phi JH, et al. Pathoembryogenesis of terminal myelocystocele: terminal balloon in secondary neurulation of the chick embryo. Childs Nerv Syst. 2013;29:1683–8.
Pang D, Zovickian J, Lee JY, Moes GS, Wang K-C. Terminal myelocystocele: surgical observations and theory of embryogenesis. Neurosurgery. 2012;70:1383–405.
Passarge E, Lenz W. Syndrome of caudal regression in infants of diabetic mothers: observations of further cases. Pediatrics. 1966;37:672–4.
Alexander E, Nashold BS. Agenesis of the sacrococcygeal region. J Neurosurg. 1956;13:507–13.
Frantz CH, Aitken GT. Complete absence of the lumbar spine and sacrum. JBJS. 1967;49-A:1531–40.
Freedman B. Congenital absence of the sacrum and coccyx. Report of a case and review of the literature. Br J Surg. 1950;37:299–303.
Hamsa WR. Congenital absence of the sacrum. Arch Surg. 1935;30:657–66.
Pang D, Hoffman HJ. Sacral agenesis with progressive neurological deficit. Neurosurgery. 1980;7:118–26.
Renshaw TS. Sacral agenesis. A classification and review of twenty-three cases. JBJS. 1978;60-A:373–83.
Sarnat HB, Case ME, Graviss R. Sacral agenesis. Neurologic and neuropathologic features. Neurology. 1976;26:1124–9.
Smith ED. Congenital sacral defects. In: Stephens FD, editor. Congenital malformations of the rectum, anus, and genito-urinary tracts. Edinburgh: E. & S. Livingstone; 1963. p. 82–105.
Rosselet P. A rare case of rachischisis with multiple malformations. Am J Roentgenol. 1955;73:235–40.
Stewart SF. Absence of sacrum with report of a case, and a review of the literature. Arch Surg. 1924;9:647–52.
Williams DI, Nixon HH. Agenesis of the sacrum. Surg Gynecol Obstet. 1957;105:84–8.
Price DL, Dooling EC, Richardson EP. Caudal dysplasia (caudal regression syndrome). Arch Neurol. 1970;23:212–20.
Rusnak SL, Driscoll SG. Congenital spinal anomalies in infants of diabetic mothers. Pediatrics. 1965;35:989–95.
Banta JV, Nichols O. Sacral agenesis. JBJS. 1969;51-A:693–703.
Blumel J, Butler MC, Evans EB, Eggers GWN. Congenital anomaly of the sacrococcygeal spine. Arch Surg. 1962;85:982–93.
Blumel J, Evans EB, Eggers GWN. Partial and complete agenesis or malformation of the sacrum with associated anomalies. JBJS. 1959;41-A:497–518.
Ignelzi RJ, Lehman AW. Lumbosacral agenesis: management and embryological implications. J Neurol Neurosurg Psychiatry. 1974;37:1273–6.
Naik DR, Lendon RG, Barson AJ. A radiological study of vertebral and rib malformations in children with myelomeningocele. Clin Radiol. 1978;29:427–30.
Lausecker H. Beitrag zu den mißbildungen des Kreuzbeines. Virchows Arch Path Anat. 1952;322:119–29.
Lichtor A. Sacral agenesis. Report of a case. Arch Surg. 1947;54:430–3.
Sinclair JG, Duren N, Rude JC. Congenital lumbosacral defect. Arch Surg. 1941;43:473–8.
Girard PM. Congenital absence of the sacrum. JBJS. 1935;17:1062–4.
Källén B, Winberg J. Caudal mesoderm pattern of anomalies: from renal agenesis to sirenomelia. Teratology. 1974;9:99–112.
Dias MS, Azizkhan RG. A novel embryonic mechanism for Currarino’s triad: inadequate dorsoventral separation of the caudal eminence from hindgut endoderm. Pediatr Neurosurg. 1998;28:223–9.
Gaskill SJ, Marlin AE. The Currarino triad: its importance in pediatric neurosurgery. Pediatr Neurosurg. 1997;25:143–6.
Lee S-C, Chun Y-S, Jung S-E, Park K-W, Kin W-K. Currarino triad: anorectal malformation, sacral bony abnormality, and presacral mass-a review of 11 cases. J Pediatr Surg. 1997;32:58–61.
Ashcraft KW, Holder TM. Congenital anal stenosis with presacral teratoma: case reports. Ann Surg. 1965;162:1091–5.
Yates VD, Wilroy RS, Whitington GL, Simmons JCH. Anterior sacral defects: an autosomal dominantly inherited condition. J Pediatr. 1983;102:239–42.
Cohn J, Bay-Nielsen E. Hereditary defect of the sacrum and coccyx with anterior sacral meningocele. Acta Paediatr Scand. 1969;58:268–74.
Ross AJ, Ruiz-Perez V, Wang Y, Hagan DM, Scherer S, Lynch SA, et al. A homeobox gene, HLXB9, is the major locus for dominantly inherited sacral agenesis. Nat Genet. 1998;20:358–61.
Mills JL. Malformations in infants of diabetic mothers. Teratology. 1982;25:385–94.
Duraiswami PK. Comparison of congenital defects induced in developing chickens by certain teratogenic agents with those caused by insulin. JBJS. 1955;37:277–94.
Landauer W. Rumplessness of chicken embryos produced by the injection of insulin and other chemicals. J Exp Zool. 1945;98:65–77.
Zwilling E. The effects of some hormones on development. Ann N Y Acad Sci. 1952;55:196–202.
Horton WEJ, Sadler TW. Effects of maternal diabetes on early embryogenesis: alterations in morphogenesis produced by the ketone body, ß-hydroxybutyrate. Diabetes. 1983;32:610–6.
Duhamel B. From the mermaid to anal imperforation: the syndrome of caudal regression. Arch Dis Child. 1961;36:152–5.
Wolff E. La Science des Monstres. Paris: Gallimard; 1948.
Gardner RJM, Nelson MM. An association of caudal malformations arising from a defect in the “axial mesoderm” developmental field. Am J Med Genet. 1986;2:37–44.
Storm-Mathisen A. Myelodysplasia with absence of sacrum. Acta Psychiatr Neurol Scand. 1954;29:145–9.
Bennett D. The T-locus of the mouse. Cell. 1975;6:441–54.
Fontanella F, van Maarle MC, de Medina R, Oostra RJ, van Rijn RR, Pajkrt E, et al. Prenatal evidence of persistent notochord and absent sacrum caused by a mutation in the T (brachyury) gene. Case Rep Obstet Gynecol. 2016;2016:7625341.
Pang D, Zovickian J, Moes GS. Retained medullary cord in humans: late arrest of secondary neurulation. Neurosurgery. 2011;68:1500–19.
Colas J-F, Schoenwolf GC. Towards a cellular and molecular understanding of neurulation. Dev Dyn. 2001;221:117–45.
Moury JD, Schoenwolf GC. Cooperative model of epithelial shaping and bending during avian neurulation: autonomous movements of the neural plate, autonomous movements of the epidermis, and interactions in the neural plate/epidermis transition zone. Dev Dyn. 1995;204:323–37.
Dias MS, McLone DG. Normal and abnormal early development of the nervous system. In: McLone DG, editor. Pediatric neurosurgery: surgery of the developing nervous system. Philadelphia: W.B. Saunders; 2001. p. 31–71.
Moore KL. The developing human. 3rd ed. Philadelphia: W.B. Saunders Co.; 1982.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Dias, M.S., Rizk, E.B. (2019). Embryology of Occult Spinal Dysraphisms. In: Tubbs, R., Oskouian, R., Blount, J., Oakes, W. (eds) Occult Spinal Dysraphism. Springer, Cham. https://doi.org/10.1007/978-3-030-10994-3_2
Download citation
DOI: https://doi.org/10.1007/978-3-030-10994-3_2
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-10993-6
Online ISBN: 978-3-030-10994-3
eBook Packages: MedicineMedicine (R0)