Kidwell Chelsea U, Su Chen-Ying, Hibi Masahiko, Moens Cecilia B
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Biology, University of Washington, Seattle, WA 98105, USA.
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Dev Biol. 2018 Jun 1;438(1):44-56. doi: 10.1016/j.ydbio.2018.03.004. Epub 2018 Mar 13.
A single Atoh1 basic-helix-loop-helix transcription factor specifies multiple neuron types in the mammalian cerebellum and anterior hindbrain. The zebrafish genome encodes three paralagous atoh1 genes whose functions in cerebellum and anterior hindbrain development we explore here. With use of a transgenic reporter, we report that zebrafish atoh1c-expressing cells are organized in two distinct domains that are separated both by space and developmental time. An early isthmic expression domain gives rise to an extracerebellar population in rhombomere 1 and an upper rhombic lip domain gives rise to granule cell progenitors that migrate to populate all four granule cell territories of the fish cerebellum. Using genetic mutants we find that of the three zebrafish atoh1 paralogs, atoh1c and atoh1a are required for the full complement of granule neurons. Surprisingly, the two genes are expressed in non-overlapping granule cell progenitor populations, indicating that fish use duplicate atoh1 genes to generate granule cell diversity that is not detected in mammals. Finally, live imaging of granule cell migration in wildtype and atoh1c mutant embryos reveals that while atoh1c is not required for granule cell specification per se, it is required for granule cells to delaminate and migrate away from the rhombic lip.
单个Atoh1碱性螺旋-环-螺旋转录因子可指定哺乳动物小脑和前脑后部的多种神经元类型。斑马鱼基因组编码三个旁系同源的atoh1基因，我们在此探索它们在小脑和前脑后部发育中的功能。利用转基因报告基因，我们发现表达斑马鱼atoh1c的细胞组织在两个不同的区域，这两个区域在空间和发育时间上都是分开的。早期的峡部表达区域产生菱脑节1中的小脑外群体，而上菱唇区域产生颗粒细胞祖细胞，这些祖细胞迁移以填充鱼小脑的所有四个颗粒细胞区域。使用基因敲除突变体，我们发现，在三个斑马鱼atoh1旁系同源物中，atoh1c和atoh1a是颗粒神经元完整补充所必需的。令人惊讶的是，这两个基因在不重叠的颗粒细胞祖细胞群体中表达，这表明鱼类利用重复的atoh1基因来产生哺乳动物中未检测到的颗粒细胞多样性。最后，对野生型和atoh1c突变体胚胎中颗粒细胞迁移的实时成像显示，虽然atoh1c本身不是颗粒细胞特化所必需的，但它是颗粒细胞从菱唇分层并迁移所必需的。
