PUBLICATION

Tfap2a and Foxd3 regulate early steps in the development of the neural crest progenitor population

Authors
Wang, W.D., Melville, D.B., Montero-Balaguer, M., Hatzopoulos, A.K., and Knapik, E.W.
ID
ZDB-PUB-111019-4
Date
2011
Source
Developmental Biology   360(1): 173-85 (Journal)
Registered Authors
Knapik, Ela W., Melville, David, Montero-Balaguer, Mercedes, Wang, Wen-Der
Keywords
neural crest induction, stem cells, Tfap2a, Foxd3, zebrafish
MeSH Terms
  • Animals
  • Base Sequence
  • Body Patterning
  • Bone Morphogenetic Proteins/genetics
  • Bone Morphogenetic Proteins/metabolism
  • Cell Death
  • DNA Primers/genetics
  • Embryonic Stem Cells/cytology
  • Embryonic Stem Cells/metabolism*
  • Forkhead Transcription Factors/genetics
  • Forkhead Transcription Factors/metabolism*
  • Gastrulation
  • Gene Expression Regulation, Developmental
  • Genes, p53
  • Intercellular Signaling Peptides and Proteins/genetics
  • Intercellular Signaling Peptides and Proteins/metabolism
  • Mutation
  • Neural Crest/cytology
  • Neural Crest/embryology*
  • Neural Crest/metabolism*
  • Neurogenesis
  • Transcription Factor AP-2/genetics
  • Transcription Factor AP-2/metabolism*
  • Wnt Signaling Pathway
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
21963426 Full text @ Dev. Biol.
Abstract
The neural crest is a stem cell-like population exclusive to vertebrates that gives rise to many different cell types including chondrocytes, neurons and melanocytes. Arising from the neural plate border at the intersection of Wnt and Bmp signaling pathways, the complexity of neural crest gene regulatory networks has made the earliest steps of induction difficult to elucidate. Here, we report that tfap2a and foxd3 participate in neural crest induction and are necessary and sufficient for this process to proceed. Double mutant tfap2a (mont blanc, mob) and foxd3 (mother superior, mos) mob;mos zebrafish embryos completely lack all neural crest-derived tissues. Moreover, tfap2a and foxd3 are expressed during gastrulation prior to neural crest induction in distinct, complementary, domains; tfap2a is expressed in the ventral non-neural ectoderm and foxd3 in the dorsal mesendoderm and ectoderm. We further show that Bmp signaling is expanded in mob;mos embryos while expression of dkk1, a Wnt signaling inhibitor, is increased and canonical Wnt targets are suppressed. These changes in Bmp and Wnt signaling result in specific perturbations of neural crest induction rather than general defects in neural plate border or dorso-ventral patterning. foxd3 overexpression, on the other hand, enhances the ability of tfap2a to ectopically induce neural crest around the neural plate, overriding the normal neural plate border limit of the early neural crest territory. Although loss of either tfap2 or foxd2 alters Bmp and Wnt signaling patterns, only their combined inactivation sufficiently alters these signaling gradients to abort neural crest induction. Collectively, our results indicate that tfap2a and foxd3, in addition to their respective roles in the differentiation of neural crest derivatives, also jointly maintain the balance of Bmp and Wnt signaling in order to delineate the neural crest induction domain.
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