Skip to main content
SpringerLink
Log in

Serotonin and morphogenesis

Transient expression of serotonin uptake and binding protein during craniofacial morphogenesis in the mouse

  • Published:
Anatomy and Embryology Aims and scope Submit manuscript

Summary

This study describes the timecourse of expression of low-affinity serotonin uptake sites in the developing craniofacial region of the mouse embryo. Whole mouse embryos were incubated in the presence of various serotonergic compounds followed by immunocyto-chemical localization of serotonin (5-HT) and its binding protein. In the gestational day 9 embryo (3–5 somites), 5-HT uptake was observed in the myocardium of the heart, the visceral yolk sac and foregut. A specific and transient pattern of 5-HT uptake was observed in the hindbrain neuroepithelium from day 9.5–11, where it was localized in rhombomeres 2–5 in the day 9.5 embryo. By day 10, when rhombomeres were no longer evident, uptake was present in the dorso-lateral neuroepithelium surrounding the fourth ventricle (rhombic lip; cerebellar anlage). Uptake of 5-HT was initially observed in the surface epithelium of the craniofacial region at day 10 (20–25 somites) and was greatly increased at day 11. The invaginating lens, nasal placode epithelium and otocyst also took up 5-HT at day 11. During these stages a 45 kD serotonin-binding protein (SBP) was expressed in craniofacial mesenchyme, and became progressively restricted to regions subjacent to epithelial uptake sites. These staining patterns were shown to be specific for 5-HT and SBP by their absence in embryos stained using preabsorbed antisera. The timecourse of these patterns are correlated with critical events in craniofacial morphogenesis including (1) onset of inductive epithelial-mesenchymal interactions, (2) invagination and fusion of placodal structures, (3) presence of rhombomeres, and (4) regions of low proliferative activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

5-HT :

serotonin

SBP :

serotonin binding protein

IR :

immunoreactivity

E :

embryonic day

N :

nialamide

C :

l-cysteine

pCPA :

para-chlorophenylalanine

References

  • Bailey LJ, Minkoff R, Koch WE (1988) Relative growth rates of maxillary mesenchyme in the chick embryo. J Craniofac Genet Dev Biol 8:167–177

    Google Scholar 

  • Beck F, Samani NJ, Penschow JD, Thorley B, Tregear GW, Coghlan JP (1987) Histochemical localization of IGF-I and -II mRNA in the developing rat embryo. Development 101:175–184

    Google Scholar 

  • Bee J, Thorogood P (1980) The role of tissue interactions in the skeletogenic differentiation of avian neural crest cells. Dev Biol 78:47–62

    Google Scholar 

  • Buznikov GA (1990) Neurotransmitters in embryogenesis. Soviet Scientific Rev Suppl Series, Harwood Academic Publ, Chur, Switzerland

    Google Scholar 

  • Chiquet-Ehrismann R, Mackie EJ, Pearson CA, Sakakura T (1986) Tenascin: an extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis. Cell 47:131–139

    Google Scholar 

  • Cool DR, Leibach FH, Bhalla VK, Mahesh VB, Ganapathy V (1991) Expression and cycic AMP-dependent regulation of a high-affinity serotonin transporter in the human placental choriocarcinoma cell line (JAR). J Biol Chem 266:15750–15757

    Google Scholar 

  • Figueroa AA, Pratt RM (1979) Autoradiographic study of macro-molecular synthesis in the fusion epithelium of the developing rat primary palate in vitro. J Embryol Exp Morphol 50:145–154

    Google Scholar 

  • Gardner CA, Darnell DK, Poole SJ, Ordahl CP, Barald KF (1988) Expression of engrailed-like gene during development of the early embryonic chick nervous system. J Neurosci Res 21:426–437

    Google Scholar 

  • Gatherer D, Dijke PT, Baird DT, Akhurst RJ (1990) Expression of TGF-β isoforms during first trimester human embryogenesis. Development 110:445–460

    Google Scholar 

  • Gershon MD, Liu KP, Karpiak SE, Tamir H (1983) Storage of serotonin in vivo as a complex with serotonin-binding protein in central and peripheral serotonergic neurons. J Neurosci 3:1901–1911

    Google Scholar 

  • Grobstein C (1955) Inductive interaction in the development of the mouse metanephros. J Exp Zool 130:319–340

    Google Scholar 

  • Hall BK (1980) Tissue interactions and the initiation of osteogenesis and chondrogenesis in the neural crest-derived mandibular skeleton of the embryonic mouse as seen in isolated murine tissues and in recombinations of murine and avian tissues. J Embryol Exp Morphol 58:251–264

    Google Scholar 

  • Hall BK, Hörstadius S (1988) The neural crest. Oxford University Press, New York

    Google Scholar 

  • Hannan GN, McAuslan BR (1987) Immobilized serotonin: a novel substrate for cell culture. Exp Cell Res 171:153–163

    CAS  PubMed  Google Scholar 

  • Hannan GN, Reilly W, McAuslan BR (1988) Mechanisms of serum protein binding and cell anchorage to immobilized serotonin and indole analogs. Exp Cell Res 176:49–59

    Google Scholar 

  • Heine UI, Munoz EF, Flanders KC, Ellingsworth LR, Lam HYP, Thompson NL, Roberts AB, Sporn MB (1987) Role of transforming growth factor-β in the development of the mouse embryo. J Cell Biol 105:2861–2876

    Google Scholar 

  • Holtfreter J (1968) On mesenchyme and epithelia in inductive and morphogenetic processes. In: Fleischmajer R, Billingham RE (eds) Epithelial-mesenchymal interactions. Williams & Wilkins, Baltimore, pp 1–30

    Google Scholar 

  • Hsu SM, Raine L, Fanger H (1981) Use of the avidin-biotin peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabelled antibody (PAP) procedures. J Histochem Cytochem 29:577–580

    CAS  PubMed  Google Scholar 

  • Hudson CD, Shapiro BL (1973) A radioautographic study of deoxyribonucleic acid synthesis in embryonic rat palatal shelf epithelium with reference to the concept of programmed cell death. Arch Oral Biol 18:77–84

    Google Scholar 

  • Hunt P, Whiting J, Muchamore I, Marshall H, Krumlauf R (1991a) Homeobox genes and models for patterning the hindbrain and branchial arches. Development 110 [Suppl]:187–196

    Google Scholar 

  • Hunt P, Whiting J, Nonchev S, Sham M-H, Marshall H, Graham A, Cook M, Alleman R, Rigby PWJ, Gulisano M, Faiella A, Boncinelli E, Krumlauf R (1991b) The branchial Hox code and its implications for gene regulation, patterning of the nervous system and head evolution. Development [Suppl] 2:63–77

    Google Scholar 

  • Hunt P, Wilkinson D, Krumlauf R (1991c) Patterning the vertebrate head: murine Hox 2 genes mark distinct subpopulations of premigratory and migrating cranial neural crest. Development 112:43–50

    Google Scholar 

  • Jacobson AG (1963a) The determination and positioning of the nose, lens, and ear I. Interactions within the ectoderm and between the ectoderm and underlying tissues. J Exp Zool 154:273–284

    Google Scholar 

  • Jacobson AG (1963b) The determination and positioning of the nose, lens, and ear II. The role of the endoderm. J Exp Zool 154:285–292

    Google Scholar 

  • Jacobson AG (1963c) The determination and positioning of the nose, lens, and ear III. Effects of reversing the anteroposterior axis of epidermis, neural plate and neural fold. J Exp Zool 154:293–310

    Google Scholar 

  • Källen B (1962) Mitotic patterning in the central nervous system of chick embryos; studied by a colchicine method. Z Anat Entwicklungsgesch 123:309–319

    Google Scholar 

  • Keynes R, Lumsden A (1990) Segmentation and the origin of regional diversity in the vertebrate central nervous system. Neuron 2:1–9

    Google Scholar 

  • Kimelberg HK (1986) Occurrence and functional significance of serotonin and catecholamines uptake by astrocytes. Biochem Pharmacol 35:2273–2281

    Google Scholar 

  • Kirchgessner AL, Gershon MD, Liu KP, Tamir H (1988) Costorage of serotonin binding protein with serotonin in the rat CNS. J Neurosci 8:3879–3890

    Google Scholar 

  • Koe BK, Wessman A, Welch WM, Browne RG (1983) Sertraline, 1S, 4S-N-Methyl-4-(3,4-dichlorophenyl)-1,2,3,4,-tetrahydor-1-Napthylamine, a new uptake inhibitor with selectivity for serotonin. J Pharmacol Exp Ther 226:686–700

    Google Scholar 

  • Landry CF, Youson JH, Brown IR (1990) Expression of the β-S100 gene in brain and craniofacial cartilage in the embryonic rat. Dev Neurosci 12:225–234

    Google Scholar 

  • Lauder JM (1988) Neurotransmitters as morphogens. Prog Brain Res 73:365–387

    Google Scholar 

  • Lauder JM, Krebs H (1978) Serotonin as a differentiation signal in early neurogenesis. Dev Neurosci 1:15–30

    Google Scholar 

  • Lauder JM, Zimmerman E (1988) Sites of serotonin uptake in the epithelium of the developing mouse palate, oral cavity and face: possible roles in morphogenesis? J Craniofac Genet Dev Biol 8:265–276

    Google Scholar 

  • Lauder JM, Petrusz P, Wallace JA, DiNome A, Wilkie MB, McCarthy K (1982) Combined serotonin immunocytochemistry and [3H]-thymidine autoradiography: in vivo and in vitro methods. J Histochem Cytochem 30:788–793

    Google Scholar 

  • Lauder JM, Tamir H, Sadler TW (1988) Serotonin and morphogenesis I. Sites of serotonin uptake and -binding protein immunoreactivity in the midgestation mouse embryo. Development 102:709–720

    Google Scholar 

  • Lehnert SA, Akhurst RJ (1988) Embryonic expression pattern of TGF beta type-1 RNA suggests both paracrine and autocrine mechanisms of action. Development 104:263–273

    Google Scholar 

  • Liu KP, Gershon MD, Tamir H (1985) Identification, purification, and characterization of two forms of serotonin-binding protein from rat brain. J Neurochem 44:1289–1301

    Google Scholar 

  • Lumsden A, Keynes R (1989) Segmental patterns of neuronal development in the chick hindbrain. Nature 337:424–428

    Google Scholar 

  • McAvoy JW (1980) Induction of the eye lens. Differentiation 17:137–149

    Google Scholar 

  • McGinnis W, Krumlauf R (1992) Homeobox genes and axial patterning. Cell 68:283–302

    Article  CAS  PubMed  Google Scholar 

  • Meier S (1978a) Development of the embryonic chick otic placode I. Light microscopic analysis. Anat Rec 191:447–458

    Google Scholar 

  • Meier S (1978b) Development of the embryonic chick otic placode II. Electron microscopic analysis. Anat Rec 191:459–478

    Google Scholar 

  • Morriss-Kay G, Tuckett F (1989) Immunohistochemical localisation of chondroitin sulphate proteoglycans and the effects of chondroitinase ABC in 9- to 11-day rat embryos. Development 106:787–798

    Google Scholar 

  • Murphy P, Davidson DR, Hill RE (1989) Segment-specific expression of a homeobox-containing gene in the mouse hindbrain. Nature 341:156–159

    Google Scholar 

  • Murphy P, Hill RE (1991) Expression of the mouse labial-like homeobox-containing genes, Hox 2.9 and Hox 1.6, during segmentation of the hindbrain. Development 111:61–74

    Google Scholar 

  • Nemecek GM, Coughlin SR, Handley DA, Moskowitz MA (1986) Stimulation of aortic smooth muscle cell mitogenesis by serotonin. Proc Natl Acad Sci USA 83:674–678

    Google Scholar 

  • New DAT (1978) Whole-embryo culture and the study of mammalian embryos during organogenesis. Biol Rev 53:81–122

    Google Scholar 

  • Newgreen DF, Allan IJ, Young HM, Southwell BR (1981) Accumulation of exogenous catecholamines in the neural tube and non-neural tissues of the early fowl embryo. Correlation with morphogenetic movements. Wilhelm Roux' Arch Entwick-lungsmech Org 190:320–330

    Google Scholar 

  • Nichols DH (1981) Neural crest formation in the head of the mouse embryo as observed using a new histological technique. J Embryol Exp Morphol 64:105–120

    Google Scholar 

  • Nichols DH (1987) Ultrastructure of neural crest formation in the midbrain/rostral hindbrain and preotic hindbrain regions of the mouse embryo. Am J Anat 179:143–154

    Google Scholar 

  • Noden DM (1984) Craniofacial development: new views on old problems. Anat Rec 208:1–13

    Google Scholar 

  • Noden DM (1986) Origins and patterning of craniofacial mesenchymal tissues. J Craniofac Gen Dev Biol; Suppl. 2:15–31

    Google Scholar 

  • Noden DM (1988) Interactions and fates of avian craniofacial mesenchyme. Development 103:121–140

    Google Scholar 

  • Pelton RW, Nomura S, Moses HL, Hogan BLM (1989) Expression of transforming growth factor β2 RNA during murine embryogenesis. Development 106:759–767

    Google Scholar 

  • Pelton RW, Dickinson ME, Moses HL, Hogan BLM (1990) In situ hybridization analysis of TGF β3 RNA expression during mouse development: comparative studies with TGF β1 and β2. Development 110:609–620

    Google Scholar 

  • Pratt RM, Martin GR (1975) Epithelial cell death and cyclic AMP increase during palatal development. Proc Natl Acad Sci USA 72:874–877

    Google Scholar 

  • Saber GM, Parker SB, Minkoff R (1989) Influence of epithelial-mesenchymal interaction on the viability of facial mesenchyme in vitro. Anat Rec 225:56–66

    Google Scholar 

  • Sadler TW (1979) Culture of early somite mouse embryos during organogenesis. J Ebryol Exp Morphol 49:17–25

    Google Scholar 

  • Sadler TW, New DAT (1981) Comparison of headfold stage mouse embryos cultured in rat serum versus a partially defined medium. J Embryol Exp Morphol 66:109–116

    Google Scholar 

  • Seuwen K, Magnaldo I, Pouyssegur J (1988) Serotonin stimulates DNA synthesis in fibroblasts acting through 5-HT1B receptors coupled to a G1-protein. Nature 335:254–256

    Google Scholar 

  • Shuey DL (1991) Serotonergic mechanisms in normal and abnormal craniofacial morphogenesis. PhD dissertation, University of North Carolina, Chapel Hill

    Google Scholar 

  • Shuey DL, Sadler TW, Lauder JM (1992) Serotonin as a regulator of craniofacial morphogenesis: site-specific malformations following exposure to serotonin uptake inhibitors. Teratology 46:367–378

    Google Scholar 

  • Stylianopoulou F, Efstratiadis A, Herbert J, Pintar J (1988) Pattern of the insulin-like growth factor II gene expression during rat embryogenesis. Development 103:497–506

    Google Scholar 

  • Takaya H, Watanabe T (1961) Differential proliferation of the ependyma in the developing neural tube of amphibian embryo. Embryologia 6:169–176

    Google Scholar 

  • Takuwa N, Ganz M, Takuwa Y, Sterzel RB, Rasmussen H (1989) Studies of the mitogenic effect of serotonin in rat renal mesangial cells. Am J Physiol 257:F431-F439

    Google Scholar 

  • Tamir H, Gershon MD (1990) Serotonin storing secretory vesicles. Annal NY Acad Sci 600:53–67

    Google Scholar 

  • Towle AC, Lauder JM, Joh TH (1984) Optimization of tyrosine hydroxylase immunocytochemistry in paraffin sections using pretreatment with proteolytic enzymes. J Histochem Cytochem 32:766–770

    Google Scholar 

  • Tuckett F, Lim L, Morriss-Kay GM (1985) The ontogenesis of cranial neuromeres in the rat embryo I. A scanning electron microscope and kinetic study. J Embryol Exp Morphol 87:215–228

    Google Scholar 

  • Wallace JA (1982) Monoamines in the early chick embryo: demonstration of serotonin synthesis and the regional distribution of serotonin-concentrating cells during morphogenesis. Am J Anat 165:261–276

    Google Scholar 

  • Wallace JA, Petrusz P, Lauder JM (1982) Serotonin immunocyto-chemistry in the adult and developing rat brain: methodological and pharmacological considerations. Brain Res Bull 9:117–129

    Google Scholar 

  • Wilkinson DG, Bailes JA, McMahon AP (1987) Expression of the proto-oncogene int-1 is restricted to specific neural cells in the developing mouse embryo. Cell 50:79–88

    Google Scholar 

  • Wilkinson DG, Bhatt S, Chavrier P, Bravo R, Charney P (1989a) Segment-specific expression of a zinc finger gene in the developing nervous system of the mouse. Nature 337:461–464

    Google Scholar 

  • Wilkinson DG, Bhatt S, Cook M, Boncinelli E, Krumlauf R (1989b) Segmental expression of Hox-2 homeobox genes in the developing mouse hindbrain. Nature 341:405–409

    Google Scholar 

  • Yavarone MS (1991) Prospective roles for serotonin in heart development. PhD. Dissertation, University of North Carolina, Chapel Hill

    Google Scholar 

  • Yavarone MS, Shuey DL, Sadler TW, Lauder JM (1992) Serotonin in developing placenta of the mouse embryo. Placenta (in press)

Download references

Author information

Author notes

  1. D. L. Shuey

    Present address: Developmental Toxicology Division, HERL, US-EPA, Research Triangle Park, NC, USA

Authors and Affiliations

  1. Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC, USA

    D. L. Shuey & J. M. Lauder

  2. Department of Cell Biology and Anatomy, CB7090, University of North Carolina, 27599-7090, Chapel Hill, NC, USA

    T. W. Sadler & J. M. Lauder

  3. Division of Neuroscience, New York State Psychiatric Institute, New York, NY, USA

    H. Tamir

Authors
  1. D. L. Shuey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. W. Sadler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Tamir
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. M. Lauder
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shuey, D.L., Sadler, T.W., Tamir, H. et al. Serotonin and morphogenesis. Anat Embryol 187, 75–85 (1993). https://doi.org/10.1007/BF00208198

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00208198

Key words

Search

Navigation