Engelkamp D, Rashbass P, Seawright A, van Heyningen V
MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, Scotland.
Development. 1999 Aug;126(16):3585-96. doi: 10.1242/dev.126.16.3585.
Post-mitotic neurons generated at the rhombic lip undertake long distance migration to widely dispersed destinations, giving rise to cerebellar granule cells and the precerebellar nuclei. Here we show that Pax6, a key regulator in CNS and eye development, is strongly expressed in rhombic lip and in cells migrating away from it. Development of some structures derived from these cells is severely affected in Pax6-null Small eye (Pax6(Sey)/Pax6(Sey)) embryos. Cell proliferation and initial differentiation seem unaffected, but cell migration and neurite extension are disrupted in mutant embryos. Three of the five precerebellar nuclei fail to form correctly. In the cerebellum the pre-migratory granule cell sub-layer and fissures are absent. Some granule cells are found in ectopic positions in the inferior colliculus which may result from the complete absence of Unc5h3 expression in Pax6(Sey)/Pax6(Sey) granule cells. Our results suggest that Pax6 plays a strong role during hindbrain migration processes and at least part of its activity is mediated through regulation of the netrin receptor Unc5h3.
在菱唇产生的有丝分裂后神经元进行长距离迁移，到达广泛分散的目的地，从而产生小脑颗粒细胞和小脑前核。我们在此表明，Pax6作为中枢神经系统和眼睛发育中的关键调节因子，在菱唇及其迁移出的细胞中强烈表达。在Pax6基因缺失的小眼（Pax6(Sey)/Pax6(Sey)）胚胎中，源自这些细胞的一些结构的发育受到严重影响。细胞增殖和初始分化似乎未受影响，但突变胚胎中的细胞迁移和神经突延伸受到破坏。五个小脑前核中有三个未能正常形成。在小脑中，迁移前的颗粒细胞亚层和裂沟缺失。在下丘的异位位置发现了一些颗粒细胞，这可能是由于Pax6(Sey)/Pax6(Sey)颗粒细胞中完全缺乏Unc5h3表达所致。我们的结果表明，Pax6在后脑迁移过程中发挥重要作用，其至少部分活性是通过调节网蛋白受体Unc5h3介导的。
