Montero-Balaguer, M., Lang, M.R., Sachdev, S.W., Knappmeyer, C., Stewart, R.A., De La Guardia, A., Hatzopoulos, A.K., and Knapik, E.W. (2006) The mother superior mutation ablates foxd3 activity in neural crest progenitor cells and depletes neural crest derivatives in zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists. 235(12):3199-3212.
The zebrafish mutation mother superior (mos(m188)) 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 mos(m188) mutation on zebrafish chromosome 6 in the vicinity of the foxd3 gene. Furthermore, we found that mos(m188) does not complement the sym1/foxd3 mutation, indicating that mos(m188) resides within the foxd3 locus. Injection of PAC clones containing the foxd3 gene into mos(m188) embryos restored foxd3 expression in NC progenitors and suppressed the mos(m188) phenotype. However, sequencing the foxd3 transcribed area in mos(m188) embryos did not reveal nucleotide changes segregating with the mos(m188) phenotype, implying that the mutation most likely resides outside the foxd3-coding region. Based on these findings, we propose that the mos(m188) mutation perturbs a NC-specific foxd3 regulatory element. Further analysis of mos(m188) mutants and foxd3 morphants revealed that NC cells are initially formed, suggesting that foxd3 function is required to maintain the pool of NC progenitors.