Medical Research Council Centre for Developmental Neurobiology, King's College London, London, United Kingdom.
J Neurosci. 2010 Feb 24;30(8):3048-57. doi: 10.1523/JNEUROSCI.6201-09.2010.
The granule cell layer of the cerebellum comprises the largest population of neurons in the vertebrate CNS. In amniotes, its precursors undergo a unique phase of transit amplification, regulated by Sonic hedgehog. They do so within a prominent but transient secondary proliferative epithelium, the external germinal layer, which is formed by tangential migration of precursor cells from the rhombic lip. This behavior is a hallmark of bird and mammal cerebellum development. Despite its significance for both development and disease, it is unclear whether an external germinal layer is a requirement for granule cell production or an expedient of transit amplification. Evidence for its existence in more basal vertebrates is contradictory. We therefore examined cerebellum development in the zebrafish, specifically in relation to the expression of the basic helix-loop-helix gene Atonal 1, which definitively characterizes granule cell precursors. The expression of Atoh1a-Atoh1c, in combination with patterns of proliferation and fate maps, define precursor pools at the rhombic lip and cerebellar midline but demonstrate that an external germinal layer is absent. Sonic hedgehog signaling is correspondingly absent in the zebrafish cerebellum. Sustained roof-plate-derived signals suggest that, in the absence of transit amplification, primary granule cell precursor pools are maintained throughout development. To determine whether this pattern is specific to zebrafish or reflects a more general anamniote organization, we examined the expression of similar genes in the dogfish, Scylliorhinus canicula. We show that these anamniotes share a common ground plan of granule cell production that does not include an external germinal layer.
小脑的颗粒细胞层包含脊椎动物中枢神经系统中最大的神经元群体。在羊膜动物中，其前体细胞经历了一个独特的过渡扩增阶段，由 Sonic hedgehog 调控。它们在一个突出但短暂的次级增殖上皮内进行，即外胚层，由来自菱形唇的前体细胞的切线迁移形成。这种行为是鸟类和哺乳动物小脑发育的标志。尽管它对发育和疾病都很重要，但尚不清楚外胚层是否是颗粒细胞产生的要求还是过渡扩增的权宜之计。关于其在更基础的脊椎动物中的存在的证据是相互矛盾的。因此，我们研究了斑马鱼的小脑发育，特别是与基本螺旋-环-螺旋基因 Atonal 1 的表达有关，该基因明确表征了颗粒细胞前体。Atoh1a-Atoh1c 的表达，结合增殖模式和命运图谱，定义了菱形唇和小脑中线的前体细胞池，但表明不存在外胚层。Sonic hedgehog 信号在斑马鱼小脑中相应缺失。持续的顶板衍生信号表明，在没有过渡扩增的情况下，初级颗粒细胞前体池在整个发育过程中都得到维持。为了确定这种模式是否特定于斑马鱼，或者反映了更普遍的无羊膜动物组织，我们检查了狗鲨，Scylliorhinus canicula 中类似基因的表达。我们表明，这些无羊膜动物共享不包括外胚层的颗粒细胞产生的共同基本计划。
