title: The mother superior mutation ablates foxd3 activity in neural crest progenitor cells and depletes neural crest derivatives in zebrafish.
abstract: The zebrafish mutation mother superior (mosm188) leads to a depletion of neural crest (NC) derivatives including the craniofacial cartilage skeleton, the peripheral nervous system (sympathetic neurons, dorsal root ganglia, enteric neurons), and pigment cells. The loss of derivatives is preceded by a reduction in NC-expressed transcription factors, snail1b, sox9b, sox10, and a specific loss of foxd3 expression in NC progenitor cells. We employed genetic linkage analysis and physical mapping to place the mosm188 mutation on zebrafish chromosome 6 in the vicinity of the foxd3 gene. Furthermore, we found that mosm188 does not complement the sym1/foxd3 mutation, indicating that mosm188 resides within the foxd3 locus. Injection of PAC clones containing the foxd3 gene into mosm188 embryos restored foxd3 expression in NC progenitors and suppressed the mosm188 phenotype. However, sequencing the foxd3 transcribed area in mosm188 embryos did not reveal nucleotide changes segregating with the mosm188 phenotype, implying that the mutation most likely resides outside the foxd3-coding region. Based on these findings, we propose that the mosm188 mutation perturbs a NC-specific foxd3 regulatory element. Further analysis of mosm188 mutants and foxd3 morphants revealed that NC cells are initially formed, suggesting that foxd3 function is required to maintain the pool of NC progenitors.
authors.affiliation: Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Montero-Balaguer
authors.forename: Michael R
authors.initials: MR
authors.lastname: Lang
authors.forename: Sherri Weiss
authors.initials: SW
authors.lastname: Sachdev
authors.forename: Christiane
authors.initials: C
authors.lastname: Knappmeyer
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Stewart
authors.forename: Ana
authors.initials: A
authors.lastname: De La Guardia
authors.forename: Antonis K
authors.initials: AK
authors.lastname: Hatzopoulos
authors.forename: Ela W
authors.initials: EW
authors.lastname: Knapik
mesh_terms: D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics; D020219:Chondrogenesis / Q000235:genetics; D002874:Chromosome Mapping; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D009154:Mutation; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D010641:Phenotype; D010858:Pigmentation / Q000235:genetics; D017231:Proto-Oncogene Proteins c-mos / Q000235:genetics*; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; D020319:Oligodeoxyribonucleotides, Antisense; D029867:Xenopus Proteins; C491003:foxd3b-A protein, Xenopus; C495329:Mos protein, Xenopus; D017231:Proto-Oncogene Proteins c-mos