Neural crest differentiation (WP2064)

Homo sapiens

Gene regulatory network model of cranial neural crest cell (CNCC) development, adaped from PMID: 19575671. Most interactions in the model are proposed to regulate transcription of core factors involved involved in neural crest and downstream progenitor specification. Transcriptional regulation arrows are proposed to promote transcription, unless a graphical T-bar is present at the end of the arrow (commented to be inhibitors of transcriptional regulation). Additional gene information was obtained from When citing this pathway, please reference the source publication (PMID: 19575671). Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]


Nathan Salomonis , Kristina Hanspers , Zahra Roudbari , Egon Willighagen , and Eric Weitz


last edited

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Homo sapiens



Pathway Ontology

regulatory pathway

Cell Type Ontology

neural crest derived neuron migratory cranial neural crest cell


Label Type Compact URI Comment
BMP7 GeneProduct ensembl:ENSG00000101144
RHOB GeneProduct ensembl:ENSG00000143878
MYB GeneProduct ensembl:ENSG00000118513
ITGB1 GeneProduct ensembl:ENSG00000150093
WNT1 GeneProduct ensembl:ENSG00000125084
TFAP2A GeneProduct ensembl:ENSG00000137203
ZIC1 GeneProduct ensembl:ENSG00000152977
PAX3 GeneProduct ensembl:ENSG00000135903
PAX7 GeneProduct ensembl:ENSG00000009709
DLX5 GeneProduct ensembl:ENSG00000105880
MSX1 GeneProduct ensembl:ENSG00000163132
MSX2 GeneProduct ensembl:ENSG00000120149
FOXD3 GeneProduct ensembl:ENSG00000187140
SNAI1 GeneProduct ensembl:ENSG00000124216
SNAI2 GeneProduct ensembl:ENSG00000019549
WNT3A GeneProduct ensembl:ENSG00000154342
FZD3 GeneProduct ensembl:ENSG00000104290
GSK3B GeneProduct ensembl:ENSG00000082701
CTNNB1 GeneProduct ensembl:ENSG00000168036
TCF7L1 GeneProduct ensembl:ENSG00000152284
TCF4 GeneProduct ensembl:ENSG00000196628
GBX2 GeneProduct ensembl:ENSG00000168505
AXIN2 GeneProduct ncbigene:8313
AXIN1 GeneProduct ncbigene:8312
DVL3 GeneProduct ncbigene:1857
DVL2 GeneProduct ncbigene:1856
DVL1 GeneProduct ncbigene:1855
BMP4 GeneProduct ensembl:ENSG00000125378
SMAD1 GeneProduct ensembl:ENSG00000170365
ID1 GeneProduct ensembl:ENSG00000125968
NOTCH1 GeneProduct ensembl:ENSG00000148400
DLL3 GeneProduct ensembl:ENSG00000090932
NOTCH4 GeneProduct ensembl:ENSG00000204301
NOTCH2 GeneProduct ensembl:ENSG00000134250
DLL4 GeneProduct ensembl:ENSG00000128917
NOTCH3 GeneProduct ensembl:ENSG00000074181
DLL1 GeneProduct ensembl:ENSG00000198719
HEY2 GeneProduct ensembl:ENSG00000135547
TWIST1 GeneProduct ensembl:ENSG00000122691
SOX10 GeneProduct ensembl:ENSG00000100146
FGF2 GeneProduct ensembl:ENSG00000138685
HES5 GeneProduct ensembl:ENSG00000197921
HES1 GeneProduct ensembl:ENSG00000114315
RBPJ GeneProduct ensembl:ENSG00000168214
HES5 GeneProduct ensembl:ENSG00000197921
HES1 GeneProduct ensembl:ENSG00000114315
FGFR1 GeneProduct ensembl:ENSG00000077782
FGFR2 GeneProduct ensembl:ENSG00000066468
FGFR3 GeneProduct ensembl:ENSG00000068078
ZIC5 GeneProduct ensembl:ENSG00000139800
MYC GeneProduct ensembl:ENSG00000136997
SOX9 GeneProduct ensembl:ENSG00000125398
SOX10 GeneProduct ensembl:ENSG00000100146
ISL1 GeneProduct ensembl:ENSG00000016082
CDH6 GeneProduct ensembl:ENSG00000113361
CDH2 GeneProduct ensembl:ENSG00000170558
CDH1 GeneProduct ensembl:ENSG00000039068
SOX5 GeneProduct ensembl:ENSG00000134532
ETS1 GeneProduct ensembl:ENSG00000134954
PAX3 GeneProduct ensembl:ENSG00000135903
PAX7 GeneProduct ensembl:ENSG00000009709
NFKB1 GeneProduct ensembl:ENSG00000109320
CDH7 GeneProduct ensembl:ENSG00000081138
TFAP2A GeneProduct ensembl:ENSG00000137203
SNAI1 GeneProduct ensembl:ENSG00000124216
SNAI2 GeneProduct ensembl:ENSG00000019549
FOXD3 GeneProduct ensembl:ENSG00000187140
ID1 GeneProduct ensembl:ENSG00000125968
SOX9 GeneProduct ensembl:ENSG00000125398
NFKB2 GeneProduct ensembl:ENSG00000077150
NEUROG1 GeneProduct ensembl:ENSG00000181965
SOX10 GeneProduct ensembl:ENSG00000100146
PHOX2B GeneProduct ensembl:ENSG00000109132
GFAP GeneProduct ensembl:ENSG00000131095
OLIG1 GeneProduct ensembl:ENSG00000184221
OLIG2 GeneProduct ensembl:ENSG00000205927
GJB1 GeneProduct ensembl:ENSG00000169562
ASCL1 GeneProduct ensembl:ENSG00000139352
MITF GeneProduct ensembl:ENSG00000187098
PMP22 GeneProduct ensembl:ENSG00000109099
MPZ GeneProduct ensembl:ENSG00000158887
MBP GeneProduct ensembl:ENSG00000197971
FOXD3 GeneProduct ensembl:ENSG00000187140
PAX3 GeneProduct ensembl:ENSG00000135903
LHX1 GeneProduct ensembl:ENSG00000273706
LHX2 GeneProduct ensembl:ENSG00000106689
BMP4 GeneProduct ensembl:ENSG00000125378
FGF8 GeneProduct ensembl:ENSG00000107831
FGF19 GeneProduct ensembl:ENSG00000162344
SOX10 GeneProduct ensembl:ENSG00000100146
PAX3 GeneProduct ensembl:ENSG00000135903
PAX7 GeneProduct ensembl:ENSG00000009709
SOX5 GeneProduct ensembl:ENSG00000134532
MITF GeneProduct ensembl:ENSG00000187098
HDAC1 GeneProduct ensembl:ENSG00000116478
HDAC2 GeneProduct ensembl:ENSG00000196591
HDAC3 GeneProduct ensembl:ENSG00000171720
HDAC4 GeneProduct ensembl:ENSG00000068024
HDAC5 GeneProduct ensembl:ENSG00000108840
HDAC6 GeneProduct ensembl:ENSG00000094631
HDAC7 GeneProduct ensembl:ENSG00000061273
HDAC8 GeneProduct ensembl:ENSG00000147099
HDAC9 GeneProduct ensembl:ENSG00000048052
HDAC10 GeneProduct ensembl:ENSG00000100429
HDAC11 GeneProduct ensembl:ENSG00000163517
CTBP2 GeneProduct ensembl:ENSG00000175029
DCT GeneProduct ensembl:ENSG00000080166
SOX5 GeneProduct ensembl:ENSG00000134532
SOX9 GeneProduct ensembl:ENSG00000125398
COL2A1 GeneProduct ensembl:ENSG00000139219
COL11A2 GeneProduct ensembl:ENSG00000204248
MIA GeneProduct ncbigene:8190
WNT8A GeneProduct ensembl:ENSG00000061492
HOXB1 GeneProduct ensembl:ENSG00000120094
PRTG GeneProduct ensembl:ENSG00000166450
OLIG3 GeneProduct ensembl:ENSG00000177468
TBX6 GeneProduct ensembl:ENSG00000149922
HOXA1 GeneProduct ensembl:ENSG00000105991
LHX5 GeneProduct ensembl:ENSG00000089116
TLX2 GeneProduct ensembl:ENSG00000115297
TFAP2B GeneProduct ensembl:ENSG00000008196
DMBX1 GeneProduct ensembl:ENSG00000197587
HAND1 GeneProduct ensembl:ENSG00000113196


  1. Hoxb1 neural crest preferentially form glia of the PNS. Arenkiel BR, Gaufo GO, Capecchi MR. Dev Dyn. 2003 Jul;227(3):379–86. PubMed Europe PMC Scholia
  2. Reiterated Wnt signaling during zebrafish neural crest development. Lewis JL, Bonner J, Modrell M, Ragland JW, Moon RT, Dorsky RI, et al. Development. 2004 Mar;131(6):1299–308. PubMed Europe PMC Scholia
  3. The basic helix-loop-helix olig3 establishes the neural plate boundary of the trunk and is necessary for development of the dorsal spinal cord. Filippi A, Tiso N, Deflorian G, Zecchin E, Bortolussi M, Argenton F. Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4377–82. PubMed Europe PMC Scholia
  4. AP2-dependent signals from the ectoderm regulate craniofacial development in the zebrafish embryo. Knight RD, Javidan Y, Zhang T, Nelson S, Schilling TF. Development. 2005 Jul;132(13):3127–38. PubMed Europe PMC Scholia
  5. The TLX2 homeobox gene is a transcriptional target of PHOX2B in neural-crest-derived cells. Borghini S, Bachetti T, Fava M, Di Duca M, Cargnin F, Fornasari D, et al. Biochem J. 2006 Apr 15;395(2):355–61. PubMed Europe PMC Scholia
  6. Generation and maintenance of Dmbx1 gene-targeted mutant alleles. Ohtoshi A, Bradley A, Behringer RR, Nishijima I. Mamm Genome. 2006 Jul;17(7):744–50. PubMed Europe PMC Scholia
  7. Assembling neural crest regulatory circuits into a gene regulatory network. Betancur P, Bronner-Fraser M, Sauka-Spengler T. Annu Rev Cell Dev Biol. 2010;26:581–603. PubMed Europe PMC Scholia
  8. A divergent Tbx6-related gene and Tbx6 are both required for neural crest and intermediate mesoderm development in Xenopus. Callery EM, Thomsen GH, Smith JC. Dev Biol. 2010 Apr 1;340(1):75–87. PubMed Europe PMC Scholia
  9. Protogenin, a new member of the immunoglobulin superfamily, is implicated in the development of the mouse lower first molar. Takahashi KF, Kiyoshima T, Kobayashi I, Xie M, Yamaza H, Fujiwara H, et al. BMC Dev Biol. 2010 Nov 25;10:115. PubMed Europe PMC Scholia
  10. Identification of novel Hoxa1 downstream targets regulating hindbrain, neural crest and inner ear development. Makki N, Capecchi MR. Dev Biol. 2011 Sep 15;357(2):295–304. PubMed Europe PMC Scholia