Distinct requirements for Wntless in habenular development.
Distinct requirements for Wntless in habenular development.
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DOI：
10.1016/j.ydbio.2015.06.006
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发表时间：
2015-10-15
影响因子：
2.7
通讯作者：
Halpern ME
中科院分区：
文献类型：
--
作者：
Kuan YS;Roberson S;Akitake CM;Fortuno L;Gamse J;Moens C;Halpern ME
分泌的Wnt蛋白在发育中起关键作用，包括调节细胞增殖、分化、祖细胞维持和组织形成。跨膜蛋白Wntless（Wls）是大多数Wnt分泌所必需的，并且是有效Wnt信号传导所必需的。在一个突变筛选，以确定基因的发育重要的缰核在背前脑，我们分离出一个突变的唯一wls基因的斑马鱼，并确认其身份与第二个，独立的等位基因。在纯合wls突变体中，早期胚胎发育正常，但后来缺乏腹侧缰核，形成较小的背侧缰和耳囊，有截短的颌和鳍软骨，缺乏鱼鳔。在wls突变体中，β-连环蛋白依赖性转录的报告基因的激活减少，表明经典Wnt途径的信号传导受损，并且在背侧间脑中Wnt应答基因的表达减少。Wnt信号先前与斑马鱼大脑的模式化以及两侧配对的背侧缰核之间左右（L-R）差异的产生有关。在上丘脑区域之外，wls突变体的大脑发育在很大程度上是正常的，尽管它们的尺寸减小，但背侧缰保持L-R不对称。我们发现纯合子wls突变体显示两个细胞群的减少，这两个细胞群对推测的背侧缰有贡献。结果支持不同的时间要求WLS在缰发育，并揭示了一个新的作用Wnt信号在背侧缰祖细胞的调节。
Secreted Wnt proteins play pivotal roles in development, including regulation of cell proliferation, differentiation, progenitor maintenance and tissue patterning. The transmembrane protein Wntless (Wls) is necessary for secretion of most Wnts and essential for effective Wnt signaling. During a mutagenesis screen to identify genes important for development of the habenular nuclei in the dorsal forebrain, we isolated a mutation in the sole wls gene of zebrafish and confirmed its identity with a second, independent allele. Early embryonic development appears normal in homozygous wls mutants, but they later lack the ventral habenular nuclei, form smaller dorsal habenulae and otic vesicles, have truncated jaw and fin cartilages and lack swim bladders. Activation of a reporter for β-catenin-dependent transcription is decreased in wls mutants, indicative of impaired signaling by the canonical Wnt pathway, and expression of Wnt-responsive genes is reduced in the dorsal diencephalon. Wnt signaling was previously implicated in patterning of the zebrafish brain and in the generation of left–right (L–R) differences between the bilaterally paired dorsal habenular nuclei. Outside of the epithalamic region, development of the brain is largely normal in wls mutants and, despite their reduced size, the dorsal habenulae retain L–R asymmetry. We find that homozygous wls mutants show a reduction in two cell populations that contribute to the presumptive dorsal habenulae. The results support distinct temporal requirements for Wls in habenular development and reveal a new role for Wnt signaling in the regulation of dorsal habenular progenitors.