Gofflot F, Hall M, Morriss-Kay G M
Department of Human Anatomy, University of Oxford, United Kingdom.
Int J Dev Biol. 1998 Jul;42(5):637-44.
The mouse mutant curly tail (ct) develops tail flexion defects and spina bifida as the result of delayed or failed closure of the posterior neuropore (PNP). With the aim of identifying genes involved in the chain of events resulting in defective neurulation, which can be detected at day 10.5 of development, we examined the expression patterns of a number of genes implicated in patterning of axial structures, mesoderm and neuroepithelium. The genes analyzed were Shh, HNF3alpha, HNF3beta, Brachyury, Hoxb1, Evx1, Fgf8, Wnt5a and Wnt5b. No differences could be detected between non-mutant embryos and ct/ct embryos with normal PNP size for any of these genes. Comparisons between ct/ct embryos with enlarged PNP and phenotypically normal ct/ct or nonmutant embryos showed differences only for Wnt5a. Expression of this gene was greatly reduced in the ventral caudal mesoderm and hindgut endoderm. Analysis of younger embryos revealed that prior to the stage at which embryos at risk of developing neural tube defects can be detected, the same proportion of ct/ct embryos shows reduced Wnt5a expression. The proportion of embryos showing reduced expression and almost undetectable expression of Wnt5a reflects the proportions of tail defects and spina bifida seen at later stages. We suggest that deficiency of Wnt5a signaling in the ventral caudal region tissues is an important component of the mechanism of development of the defects in affected curly tail mutant mice, and that it is causally related to decreased cell proliferation within the ventral caudal region. A possible relationship between decreased Wnt5a expression and reduced levels of heparan sulphate proteoglycan is discussed.
小鼠突变体卷尾（ct）由于后神经孔（PNP）闭合延迟或失败而出现尾部弯曲缺陷和脊柱裂。为了确定参与导致神经胚形成缺陷的一系列事件的基因，这些缺陷在发育第10.5天可被检测到，我们研究了一些与轴向结构、中胚层和神经上皮模式形成有关的基因的表达模式。分析的基因有Shh、HNF3α、HNF3β、Brachyury、Hoxb1、Evx1、Fgf8、Wnt5a和Wnt5b。对于这些基因中的任何一个，在非突变胚胎和PNP大小正常的ct/ct胚胎之间未检测到差异。将PNP扩大的ct/ct胚胎与表型正常的ct/ct或非突变胚胎进行比较，仅发现Wnt5a存在差异。该基因在腹侧尾中胚层和后肠内胚层中的表达大大降低。对较年轻胚胎的分析表明，在可检测到有神经管缺陷风险的胚胎阶段之前，相同比例的ct/ct胚胎显示Wnt5a表达降低。显示Wnt5a表达降低和几乎检测不到的胚胎比例反映了后期出现的尾部缺陷和脊柱裂的比例。我们认为，腹侧尾区组织中Wnt5a信号的缺乏是受影响的卷尾突变小鼠缺陷发育机制的一个重要组成部分，并且它与腹侧尾区内细胞增殖减少存在因果关系。还讨论了Wnt5a表达降低与硫酸乙酰肝素蛋白聚糖水平降低之间的可能关系。
