UNSW Embryology

Neural Crest- Generation 1

• Chicken Studies
• Bronner-Fraser M PNAS 1996 Sep 3;93(18):9352-7
• demonstrate that they are not a segregated population
• Interactions between the neural plate and epidermis can generate neural crest cells, since juxtaposition of these tissues at early stages results in the formation of neural crest cells at the interface.
  • At cranial levels, neuroepithelial cells can regulate to generate neural crest cells when the endogenous neural folds are removed, probably via interaction of the remaining neural tube with the epidermis.
  • progenitor cells in the neural folds are multipotent, having the ability to form multiple ectodermal derivatives, including epidermal, neural crest, and neural tube cells the neural crest is an induced population that arises by interactions between the neural plate and the epidermis;
  • the competence of theneural plate to respond to inductive interactions changes as a function of embryonic age.

Neural Crest- Generation 2

• At cranial levels, neuroepithelial cells can regulate to generate neural crest cells when the endogenous neural folds are removed, probably via interaction of the remaining neural tube with the epidermis.
• progenitor cells in the neural folds are multipotent, having the ability to form multiple ectodermal derivatives, including epidermal, neural crest, and neural tube cells
• the neural crest is an induced population that arises by interactions between the neural plate and the epidermis;
• the competence of theneural plate to respond to inductive interactions changes as a function of embryonic age.

Neural Crest Derivatives

• migrate throughout the embryo and give rise to many different cells
• see table in class notes
• ganglia
• cranial, dorsal root, sympathetic trunk
• celiac, renal, plexus in GIT
• glia, schwann cells
• melanocytes (skin)
• adrenal medulla (chromaffin cells)

Neural Crest-Differentiation

• Begins in cranial region when still neural fold
• In spinal cord from d 22 until d26
• after closure of caudal neuropore
• rostro-caudal gradient of differentiation

Neural Crest-Head (see also Head Development Notes)

mesencephalon and caudal proencephalon

• parasympathetic ganglia CN III
• connective tissue around eye and nerve
• head mesenchyme
• pia and arachnoid mater
• dura from mesoderm

Neural Crest-Head

mesencephalon and rhombencephalon

• pharayngeal arches
• look at practical notes on neck and head.
• cartilage rudiments (nose, face, middle ear)
• face
• dermis, smooth muscle and fat
• odontoblasts of developing teeth

 

Neural Crest-Head

rhombencephalon

• C cells of thyroid
• cranial nerve ganglia
• neurons and glia
• parasympathetic of VII, IX, X
• sensory ganglia of V, VII, VIII, IX, X

 

Neural Crest- Spinal Cord

• peripheral nervous system
• dorsal root ganglia (sensory N)
• parasympathetic ganglia
• sympathetic ganglia
• motoneurons in both ganglia
• all associated glia

Neural Crest- Migration

• Larsen- Chapter 5 p 107
• LeDouarin 80's
• Development of the peripheral Nervous system from the neural crest
• Ann Rev Cell Biol 4 p375
  • transplantation experiments in chicken/quail
  • nucleoli to differentiate different species
  • can follow path of migration of transplanted cells
  • now molecularly tag neural crest cells (LacZ)

Neural Crest- Migration 1

• Living Zebrafish Studies
• (Jesuthasan Development 1996 Jan;122(1):381-9
  • Neural crest cells in the trunk of vertebrate embryos have a choice of pathways after emigrating from the neural tube: they can migrate in either the medial pathway between somites and neural tube, or the lateral pathway between somites and epidermis.
  • In zebrafish embryos, the first cells to migrate all choose the medial pathway.
  • High resolution imaging of cells in living embryos suggests that neuralcrest cells do so because of repulsion by somites: cells take the medial pathway because the lateral somite surface triggers a paralysis and retraction of protrusions (contact inhibition or collapse) when the medial surface does not.
  • Partial deletion of somites, using the spadetail mutation allows precocious entry into the lateral pathway, but only where somites are absent, supporting the notion that an inhibitory cue on somites delays entry.

 

Neural Crest- Migration 2

• Primates
• N-CAM labelling of cranial neural crest cells (Peterson, Anatomy & Embryology 1996 Sep;194(3):235-46
  • At stage 10 (8-11 somites), crest emigration occurred in areas of unfused neural folds through focal disruptions in the neuroepithelial basement membrane in both the rostral and pre-otic regions, although there was little evidence of crest migration in the post-otic hindbrain. By stage 11 (16-17 somites), the neural folds were fused (pre- and post-otic hindbrain) or in the process of fusing (rostral hindbrain), yet crest cell emigration was apparent in all three areas through discontinuities in the basement membrane. Emigration was essentially complete at stage 12 (21 somites) as indicated by nearly continuous cranial neural tube basement membranes. At this stage the pre-ganglia (trigeminal, facioacoustic and glossopharyngeal) were consistently stained with N-CAM.

 

Use cell surface markers and ECM adhesive proteins

• laminin and collagen-IV in neuroepithelial basement membranes
• Neural Crest- Migration
• Neural crest cells migrate
• + on specific adhesive pathways
• laminin

Differential neural crest cell attachment and migration on avian laminin isoforms.

• Isolated neural crest cells differentially attached and migrated on these laminin isoforms, showing a clear preference for Laminin-G (gizzard tissue) over Laminin-alpha x (heart tissue).
• fibronectin
• T-cadherin (truncated cadherin, Ca dependent adhesion molecules)

ECM inhibitor pathways

• Aggrecans and PG-M/versicans represent two newly defined families of hyaluronan-binding proteoglycans
• S103L chondroitin sulfate proteoglycan.

Other Factors

• High glucose concentration inhibits migration of rat cranial neural crest cells in vitro.
• may explain some teratogenic effects of diabetic pregnancy

• Selected Lists of References from PubMed March 1999 search results are available for School of Anatomy computers without internet access. Computers with internet access can search from either Page 2 or PubMed Internet Access
  • Selected Research Articles and Reviews

• Martín García-Castro, Marianne Bronner-Fraser Induction and differentiation of the neural crest Current Opinion in Cell Biology 1999, 11:695-698.
  • excellent recent review on liver development. (source for references cited below)
• Baker CV, Bronner-Fraser M:
  The origins of the neural crest Part I: Embryonic induction.
  Mech Dev 1997, 69: 3&endash;11.
• Groves AK, Bronner-Fraser M:
  Neural crest diversification.
  Curr Top Dev Biol 1999, 43: 221&endash;258.
• LaBonne C, Bronner-Fraser M: Molecular mechanisms of neural crest formation. In Annu Rev Cell 1999, in press.
• Anderson DJ:
  Cellular and molecular biology of neural crest cell lineage determination.
  Trends Genet 1997, 13: 276&endash;280.
• Lee KJ, Jessell TM:
  The specification of dorsal cell fates in the vertebrate central nervous system.
  Annu Rev Neurosci 1999, 22: 261&endash;294.
• Vaglia JL, Hall BK:
  Regulation of neural crest cell populations: occurrence, distribution and underlaying mechanisms.
  Int J Dev Biol 1999, 43: 95&endash;110.
• Bronner-Fraser M, Fraser SE:
  Cell lineage analysis reveals multipotency of some avian neural crest cells.
  Nature 1988, 335: 161&endash;164.
• Bronner-Fraser M, Fraser S:
  Developmental potential of avian trunk neural crest cells in situ.
  Neuron 1989, 3: 755&endash;766.
• Artinger KB, Chitnis AB, Mercola M, Driever W:
  Zebrafish narrowminded suggests a genetic link between formation of neural crest and primary sensory neurons.
  Development 1999, 126: 3969&endash;3979.
• Selleck MA, Bronner-Fraser M:
  Origins of the avian neural crest: the role of neural plate-epidermal interactions.
  Development 1995, 121: 525&endash;538.
• Bonstein L, Elias S, Frank D:
  Paraxial-fated mesoderm is required for neural crest induction in Xenopus embryos.
  Development 1998, 192: 156&endash;168.
• Basler K, Edlund T, Jessell TM, Yamada T:
  Control of cell pattern in the neural tube: regulation of cell differentiation by dorsalin-1, a novel TGF beta family member.
  Cell 1993, 73: 687&endash;702.
• Liem KF, Tremml G Jr, Roelink H, Jessell TM:
  Dorsal differentiation of neural plate cells induced by BMP-mediated signals from epidermal ectoderm.
  Cell 1995, 82: 969&endash;979.
• Liem KF, Tremml G Jr, Jessell TM:
  A role for the roof plate and its resident TGFbeta-related proteins in neuronal patterning in the dorsal spinal cord.
  Cell 1997, 91: 127&endash;138.
• • Selleck MA, Garcia-Castro MI, Artinger KB, Bronner-Fraser M:
  Effects of Shh and Noggin on neural crest formation demonstrate that BMP is required in the neural tube but not ectoderm.
  Development 1998, 125: 4919&endash;4930.
• LaBonne C, Bronner-Fraser M:
  Neural crest induction in Xenopus: evidence for a two-signal model.
  Development 1998, 125: 2403&endash;2414.
• Ikeya M, Lee SM, Johnson JE, McMahon AP, Takada S:
  Wnt signalling required for expansion of neural crest and CNS progenitors.
  Nature 1997, 389: 966&endash;970.
• Dorsky RI, Moon RT, Raible DW:
  Control of neural crest cell fate by the Wnt signalling pathway.
  Nature 1998, 396: 370&endash;373.
• Saint-Jeannet JP, He X, Varmus HE, Dawid IB:
  Regulation of dorsal fate in the neuraxis by Wnt-1 and Wnt-3a.
  Proc Natl Acad Sci USA 1997, 94: 13713&endash;13718.
• Chang C, Hemmati-Brivanlou A:
  Neural crest induction by Xwnt7B in Xenopus.
  Dev Biol 1998, 194: 129&endash;134.
• Bang AG, Papalopulu N, Goulding MD, Kintner C:
  Expression of pax-3 in the lateral neural plate is dependent on a wnt-mediated signal from posterior nonaxial mesoderm.
  Dev Biol 1999, 212: 366&endash;380.
• Akitaya T, Bronner-Fraser M:
  Expression of cell adhesion molecules during initiation and cessation of neural crest cell migration.
  Dev Dyn 1992, 194: 12&endash;20.
• Nakagawa S, Takeichi M:
  Neural crest cell&endash;cell adhesion controlled by sequential and subpopulation-specific expression of novel cadherins.
  Development 1995, 12: 1321&endash;1332.
• Nakagawa S, Takeichi M:
  Neural crest emigration from the neural tube depends on regulated cadherin expression.
  Development 1998, 125: 2963&endash;2971.
• Erickson CA, Perris R:
  The role of cell&endash;cell and cell&endash;matrix interactions in the morphogenesis of the neural crest.
  Dev Biol 1993, 159: 60&endash;74.
• Liu JP, Jessell TM:
  A role for rhoB in the delamination of neural crest cells from the dorsal neural tube.
  Development 1998, 125: 5055&endash;5067.
• Krull CE, Lansford R, Gale NW, Collazo A, Marcelle C, Yancopoulos GD, Fraser SE, Bronner-Fraser M:
  Interactions of Eph-related receptors and ligands confer rostrocaudal pattern to trunk neural crest migration.
  Curr Biol 1997, 7: 571&endash;580.
• Wang HU, Anerson DJ:
  Eph family transmembrane ligands can mediate repulsive guidance of trunk neural crest migration and motor axon outgrowth.
  Neuron 1997, 18: 383&endash;396.
• Debby-Brafman A, Burstyn-Cohen T, Klar A, Kalcheim C:
  F-Spondin, expressed in somite regions avoided by neural crest cells, mediates inhibition of distinct somite domains to neural crest migration.
  Neuron 1999, 22: 475&endash;488.
• Eickholt BJ, Mackenzie SL, Graham A, Walsh FS, Doherty P:
  Evidence for collapsin-1 functioning in the control of neural crest migration in both trunk and hindbrain regions.
  
• Stemple DL, Anderson DJ:
  Isolation of a stem cell for neurons and glia from the mammalian neural crest.
  Cell 1992, 71: 973&endash;985.
• Morrison SJ, White PM, Zock C, Anderson DJ:
  Prospective identification, isolation by flow cytometry, and in vivo self-renewal of multipotent mammalian neural crest stem cells.
  Cell 1999, 96: 737&endash;749.
• Sharma K, Korade Z, Frank E:
  Late-migrating neuroepithelial cells from the spinal cord differentiate into sensory ganglion cells and melanocytes.
  Neuron 1995, 14: 143&endash;152.
• Korade Z, Frank E:
  Restriction in cell fates of developing spinal cord cells transplanted to neural crest pathways.
  J Neurosci 1996, 16: 7638&endash;7648.
• Keirstead HS, Ben-Hur T, Rogister B, O'Leary MT, Dubois-Dalcq M, Blakemore WF:
  Polysialylated neural cell adhesion molecule-positive CNS precursors generate both oligodendrocytes and schwann cells to remyelinate the CNS after transplantation.
  J Neurosci 1999, 19: 7529&endash;7536.
• Kalyani A, Hobson K, Rao MS:
  Neuroepithelial stem cells from the embryonic spinal cord: isolation, characterization, and clonal analysis.
  Dev Biol 1997, 186: 202&endash;223.
• Kalyani AJ, Piper D, Mujtaba T, Lucero MT, Rao MS:
  Spinal cord neuronal precursors generate multiple neuronal phenotypes in culture.
  J Neurosci 1998, 18: 7856&endash;7868.
• Shah NM, Groves AK, Anderson DJ:
  Alternative neural crest cell fates are instructively promoted by TGFbeta superfamily members.
  Cell 1996, 85: 331&endash;343.
• Varley JE, Wehby R.G, Rueger DC, Maxwell GD:
  Number of adrenergic and islet-1 immunoreactive cells is increased in avian trunk neural crest cultures in the presence of human recombinant osteogenic protein-1.
  Dev Dyn 1995, 203: 434&endash;447.
• Reissmann E, Ernsberger U, Francis-West PH, Rueger D, Brickell P, Rohrer H:
  Involvement of bone morphogenetic protein-4 and bone morphogenetic protein-7 in the differentiation of the adrenergic phenotype in developing sympathetic neurons.
  Development 1996, 122: 2079&endash;2088.
• Moore MW, Klein RD, Farinas I, Sauer H, Armanini M, Phillips H, Reichardt LF, Ryan AM, Carver-Moore K, Rosenthal A:
  Renal and neuronal abnormalities in mice lacking GDNF.
  Nature 1996, 382: 76&endash;79.
• Pichel JG, Shen L, Sheng HZ, Granholm AC, Drago J, Grinberg A, Lee EJ, Huang SP, Saarma M, Hoffer BJ, Sariola H, Westphal H:
  Defects in enteric innervation and kidney development in mice lacking GDNF.
  Nature 1996, 382: 73&endash;76.
• Sanchez MP, Silos-Santiago I, Frisen J, He B, Lira SA, Barbacid M:
  Renal agenesis and the absence of enteric neurons in mice lacking GDNF.
  Nature 1996, 382: 70&endash;73.
• Schuchardt A, D'Agati V, Larsson-Blomberg L, Costantini F, Pachnis V:
  Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret.
  Nature 1994, 367: 380&endash;383.
• Durbec PL, Larsson-Blomberg LB, Schuchardt A, Costantini F, Pachnis V:
  Common origin and developmental dependence on c-ret of subsets of enteric and sympathetic neuroblasts.
  Development 1996, 122: 349&endash;358.
• Cacalano G, Farinas I, Wang LC, Hagler K, Forgie A, Moore M, Armanini M, Phillips H, Ryan AM, Reichardt LF et al.:
  GFRalpha1 is an essential receptor component for GDNF in the developing nervous system and kidney.
  Neuron 1998, 21: 53&endash;62.
• Enomoto H, Araki T, Jackman A, Heuckeroth RO, Snider WD, Johnson EM Jr, Milbrandt J:
  GFR alpha1-deficient mice have deficits in the enteric nervous system and kidneys.
  Neuron 1998, 21: 2.
• Britsch S, Li L, Kirchhoff S, Theuring F, Brinkmann V, Birchmeier C, Riethmacher D:
  The ErbB2 and ErbB3 receptors and their ligand, neuregulin-1, are essential for development of the sympathetic nervous system.
  Genes Dev 1998, 12: 1824&endash;1836.
• Pattyn A, Morin X, Cremer H, Goridis C, Brunet JF:
  The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives.
  Nature 1999, 399: 366&endash;370.
• Lo L, Tiveron MC, Anderson DJ:
  MASH1 activates expression of the paired homeodomain transcription factor Phox2a, and couples pan-neuronal and subtype-specific components of autonomic neuronal identity.
  Development 1998, 125: 609&endash;620.
• Lo L, Morin X, Brunet JF, Anderson DJ:
  Specification of neurotransmitter identity by Phox2 proteins in neural crest stem cells.
  Neuron 1999, 22: 693&endash;705.
• Opdecamp K, Nakayama A, Nguyen MT, Hodgkinson CA, Pavan WJ, Arnheiter H:
  Melanocyte development in vivo and in neural crest cell cultures: crucial dependence on the Mitf basic-helix-loop-helix-zipper transcription factor.
  Development 1997, 124: 2377&endash;2386.
• Perez SE, Rebelo S, Anderson DJ:
  Early specification of sensory neuron fate revealed by expression and function of neurogenins in the chick embryo.
  Development 1999, 126: 1715&endash;1728.

Neural Crest Terms

Glossary of Terms

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