The mother superior mutation ablates foxd3 activity in neural crest progenitor cells and depletes neural crest derivatives in zebrafish
The mother superior mutation ablates foxd3 activity in neural crest progenitor cells and depletes neural crest derivatives in zebrafish
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DOI：
10.1002/dvdy.20959
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发表时间：
2006-12-01
影响因子：
2.5
通讯作者：
Knapik, Ela W.
中科院分区：
文献类型：
--
作者：
Montero-Balaguer, Mercedes;Lang, Michael R.;Knapik, Ela W.
斑马鱼突变母superior （mos(m188)）导致神经嵴（NC）衍生物的耗损，包括颅面软骨骨架、周围神经系统（交感神经元、背根神经节、肠神经元）和色素细胞。在NC祖细胞中，NC表达的转录因子snail1b、sox9b、sox10的表达减少，以及foxd3表达的特异性减少，是其衍生物缺失的前兆。我们利用遗传连锁分析和物理定位将斑马鱼6号染色体上的mos（m188）突变定位在foxd3基因附近。此外，我们发现mos（m188）不补充sym1/foxd3突变，表明mos（m188）位于foxd3位点。将含有foxd3基因的PAC克隆注射到mos（m188）胚胎中，可以恢复NC祖细胞中foxd3的表达，抑制mos（m188）表型。然而，对mos（m188）胚胎中foxd3转录区进行测序并没有发现与mos（m188）表型分离的核苷酸变化，这意味着突变很可能位于foxd3编码区之外。基于这些发现，我们提出mos（m188）突变干扰nc特异性foxd3调控元件。对mos（m188）突变体和foxd3突变体的进一步分析表明，NC细胞是最初形成的，这表明foxd3的功能是维持NC祖细胞池的必要条件。
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.