Neural Crest - Peripheral Nervous System

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Human embryo neural crest cells (stage 11)

The neural crest are bilaterally paired strips of cells arising in the ectoderm at the margins of the neural tube. These cells migrate to many different locations and differentiate into many cell types within the embryo. This means that many different systems (neural, skin, teeth, head, face, heart, adrenal glands, gastrointestinal tract) will also have a contribution fron the neural crest cells.

In the body region, neural crest cells also contribute the peripheral nervous system (both neurons and glia) consisting of sensory ganglia (dorsal root ganglia), sympathetic and parasympathetic ganglia and neural plexuses within specific tissues/organs.

In the head region, neural crest cells migrate into the pharyngeal arches (as shown in movie below) forming ectomesenchyme contributing tissues which in the body region are typically derived from mesoderm (cartilage, bone, and connective tissue).General neural development is also covered in Neural Notes.

Neural Crest Links: neural crest | Lecture - Early Neural | Lecture - Neural Crest Development | Lecture Movie | Schwann cell | adrenal | melanocyte | peripheral nervous system | enteric nervous system | cornea | cranial nerve neural crest | head | skull | cardiac neural crest | Nicole Le Douarin | Neural Crest Movies | neural crest abnormalities | Category:Neural Crest
Student Projects 2023: 1 Patterning neural border and NC | 2 NPB NEUcrest | 3 EMT and NC | 4 miRNA and NC | 5 Adrenal Gland and NC | 6 Melanocyte & Melanoma | 7 Neurocristopathies | Neural Crest
These projects are the sole work of undergraduate science students and may contain errors in fact or descriptions.

Historic Embryology - Neural Crest  
1879 Olfactory Organ | 1905 Cranial and Spinal Nerves | 1908 10 mm Peripheral | 1910 Mammal Sympathetic | 1920 Human Sympathetic | 1928 Cranial ganglia | 1939 10 Somite Embryo | 1942 Origin | 1957 Adrenal

Some Recent Findings

  • Neuronal differentiation in the developing human spinal ganglia[1] "The spatiotemporal developmental pattern of the neural crest cells differentiation towards the first appearance of the neuronal subtypes was investigated in developing human spinal ganglia between the 5th -10th developmental week using immunohistochemistry and immunofluorescence methods. First NF200 (neurofilament-200, likely-myelinated mechanoreceptors) and isolectin-B4 positive neurons (likely-unmyelinated nociceptors) appeared already in the 5/6th developmental week and their number subsequently increased during progression of development. Proportion of NF200 positive cells was higher in the ventral parts of the spinal ganglia than in the dorsal parts, particularly during the 5/6th and 9/10th developmental weeks (Mann-Whitney, p=0.040 and p=0.003). NF200 and IB4 co-localized during the whole investigated period. Calcitonin gene-related peptide (CGRP, nociceptive responses), vanilloid-receptor-1 (VR1, polymodal nociceptors) and calretinin (calcium signalling) cell immunoreactivity first appeared in the 6th and 8th week, respectively, especially in the dorsal parts of the spinal ganglia. VR1 and CGRP co-localized with NF00 during the whole investigated period. Our results indicate the high potential of early differentiated neuronal cells, which slightly decreased with progression of spinal ganglia differentiation. On the contrary, the number of neuronal subtypes displayed increasing differentiation at later developmental stage."
  • The role of the transcription factor Rbpj in the development of dorsal root ganglia[2] "The dorsal root ganglion (DRG) is composed of well-characterized populations of sensory neurons and glia derived from a common pool of neural crest stem cells (NCCs), and is a good system to study the mechanisms of neurogenesis and gliogenesis. Notch signaling is known to play important roles in DRG development, but the full scope of Notch functions in mammalian DRG development remains poorly understood."
  • Cranial neural crest migration: new rules for an old road.[3] "In this review, we discuss recent cellular and molecular discoveries of the CNCC migratory pattern. We focus on events from the time when CNCCs encounter the tissue adjacent to the neural tube and their travel through different microenvironments and into the branchial arches. We describe the patterning of discrete cell migratory streams that emerge from the hindbrain, rhombomere (r) segments r1-r7, and the signals that coordinate directed migration."
More recent papers  
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Search term: Peripheral Nervous System Development

<pubmed limit=5>Peripheral Nervous System Development</pubmed>

Search term: Dorsal Root Ganglia Development

<pubmed limit=5>Dorsal Root Ganglia Development</pubmed>

Search term: Sympathetic Development

<pubmed limit=5>Sympathetic Development</pubmed>

Neural Crest Migration

<html5media height="380" width="410">File:Chicken-neural crest migration 01.mp4</html5media>

Movie Source: Original Neural Crest movies kindly provided by Paul Kulesa.[4]

Related Movies: Migration 01 | Migration 02 | Migration 03 | Migration 04 | Migration 05 | Migration 06 | Migration 07

Development Overview

The following cranial and trunk data is based upon 185 serially sectioned staged (Carnegie) human embryos.[5]

Cranial Neural Crest

  • stage 9 - an indication of mesencephalic neural crest
  • stage 10 - trigeminal, facial, and postotic components
  • stage 11 - crest-free zones are soon observable in rhombomere 1, 3, and 5
  • stage 12 - rhombomeres 6 and 7 neural crest migrate to pharyngeal arch 3 and then rostrad to the truncus arteriosus
  • stage 13 - nasal crest and the terminalis-vomeronasal complex are last of the cranial crest to appear

stages 9-14 - otic vesicle primordium descends

Trunk Neural Crest

Spinal ganglia increase in number over time and are in phase with the somites, though not their centre. There are 3 migratory pathways: ventrolateral between dermatomyotome and sclerotome, ventromedial between neural tube and sclerotomes, and lateral between surface ectoderm and dermatomyotome.

  • stage 13 - about 19 present
  • stage 14 - about 33 present
  • stage 15-23 - 30–35 ganglia

Animal Models


SEMA3A and NRP1 control trunk Neural Crest Cell migration to organise Mouse PNS neurons
Model of trunk Neural Crest Cell migration to organise Mouse PNS neurons[6]

(A and B) NCC migration pathways at 9.5 dpc.

  • A - In wild-types, only a few intermediate wave NCCs are NRP1-negative (green) and travel alongside intersomitic and perisomitic vessels (red). Rather, most NCCs are NRP1-positive (yellow) and are channeled into the anterior sclerotome by repulsive SEMA3A signals. Accordingly, Sema3A (blue) is expressed in 2 domains, a narrow stripe in the dermomyotome adjacent to the preceding intersomitic furrow, and a broader domain in the posterior dermomyotome that extends into the posterior sclerotome.
  • B - In the absence of NRP1 signaling, intermediate wave NCCs are blind to SEMA3A (now shown in gray) and preferentially migrate alongside intersomitic blood vessels (red), similar to early wave NCCs. (C and D) Peripheral neuron position in wild-types and Nrp1-null mutants at 11.5 dpc reflects the migratory patterns of their NCC precursors.
  • C - In wild-types, sensory neurons condense into segmentally arranged dorsal root ganglia in the anterior sclerotome of the somites, while sympathetic neurons form paired, but nonsegmented primary sympathetic cords next to the dorsal aorta.
  • D - In the absence of SEMA3A/NRP1 signaling, sensory and sympathetic neurons differentiate in ectopic positions corresponding to the earlier position of their NCC precursors. Consequently, both the segmentation of the sensory system and the assembly of the sympathetic cords are disrupted.

Figure and text modified from[6]

Trunk neural crest migration.jpg

Abbreviations: da, dorsal aorta; dm, dermomyotome; isv, intersomitic vessel; psv, perisomitic vessel; pcv, posterior cardinal vein; scl, sclerotome.


  1. Vukojevic K, Filipovic N, Tica Sedlar I, Restovic I, Bocina I, Pintaric I & Saraga-Babic M. (2016). Neuronal differentiation in the developing human spinal ganglia. Anat Rec (Hoboken) , 299, 1060-72. PMID: 27225905 DOI.
  2. Hu ZL, Shi M, Huang Y, Zheng MH, Pei Z, Chen JY, Han H & Ding YQ. (2011). The role of the transcription factor Rbpj in the development of dorsal root ganglia. Neural Dev , 6, 14. PMID: 21510873 DOI.
  3. Kulesa PM, Bailey CM, Kasemeier-Kulesa JC & McLennan R. (2010). Cranial neural crest migration: new rules for an old road. Dev. Biol. , 344, 543-54. PMID: 20399765 DOI.
  4. Kulesa PM & Fraser SE. (2000). In ovo time-lapse analysis of chick hindbrain neural crest cell migration shows cell interactions during migration to the branchial arches. Development , 127, 1161-72. PMID: 10683170
  5. O'Rahilly R & Müller F. (2007). The development of the neural crest in the human. J. Anat. , 211, 335-51. PMID: 17848161 DOI.
  6. 6.0 6.1 Schwarz Q, Maden CH, Vieira JM & Ruhrberg C. (2009). Neuropilin 1 signaling guides neural crest cells to coordinate pathway choice with cell specification. Proc. Natl. Acad. Sci. U.S.A. , 106, 6164-9. PMID: 19325129 DOI.


Krispin S, Nitzan E & Kalcheim C. (2010). The dorsal neural tube: a dynamic setting for cell fate decisions. Dev Neurobiol , 70, 796-812. PMID: 20683859 DOI.

Ernsberger U. (2009). Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia. Cell Tissue Res. , 336, 349-84. PMID: 19387688 DOI.

Sarnat HB & Flores-Sarnat L. (2005). Embryology of the neural crest: its inductive role in the neurocutaneous syndromes. J. Child Neurol. , 20, 637-43. PMID: 16225807 DOI.

Chen HH, Hippenmeyer S, Arber S & Frank E. (2003). Development of the monosynaptic stretch reflex circuit. Curr. Opin. Neurobiol. , 13, 96-102. PMID: 12593987

Schober A & Unsicker K. (2001). Growth and neurotrophic factors regulating development and maintenance of sympathetic preganglionic neurons. Int. Rev. Cytol. , 205, 37-76. PMID: 11336393


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Search Pubmed: Peripheral Neural Development | Dorsal Root Ganglia Development | Sympathetic Neural Development | Parasympathetic Neural Development | Neural Crest Development

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