lockjaw encodes a zebrafish tfap2a required for early neural crest development.
The neural crest is a uniquely vertebrate cell type that gives rise to much of the craniofacial skeleton, pigment cells and peripheral nervous system, yet its specification and diversification during embryogenesis are poorly understood. Zebrafish homozygous for the lockjaw (low) mutation show defects in all of these derivatives and we show that low (allelic with montblanc) encodes a zebrafish tfap2a, one of a small family of transcription factors implicated in epidermal and neural crest development. A point mutation in low truncates the DNA binding and dimerization domains of tfap2a, causing a loss of function. Consistent with this, injection of antisense morpholino oligonucleotides directed against splice sites in tfap2a into wild-type embryos produces a phenotype identical to low. Analysis of early ectodermal markers revealed that neural crest specification and migration are disrupted in low mutant embryos. TUNEL labeling of dying cells in mutants revealed a transient period of apoptosis in crest cells prior to and during their migration. In the cranial neural crest, gene expression in the mandibular arch is unaffected in low mutants, in contrast to the hyoid arch, which shows severe reductions in dlx2 and hoxa2 expression. Mosaic analysis, using cell transplantation, demonstrated that neural crest defects in low are cell autonomous and secondarily cause disruptions in surrounding mesoderm. These studies demonstrate that low is required for early steps in neural crest development and suggest that tfap2a is essential for the survival of a subset of neural crest derivatives.
Knight
Robert D
RD
Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA.
Nair
Sreelaja
S
Nelson
Sarah S
SS
Afshar
Ali
A
Javidan
Yashar
Y
Geisler
Robert
R
Rauch
Gerd-Joerg
GJ
Schilling
Thomas F
TF
D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement; D002470:Cell Survival; D017690:Cell Transplantation; D003001:Cloning, Molecular; D019465:Craniofacial Abnormalities; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009432:Neural Crest / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010858:Pigmentation; D016415:Sequence Alignment; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins
D004268:DNA-Binding Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D029961:Zebrafish Proteins; C493676:tfap2a protein, zebrafish