The external granule layer (EGL) is a transient proliferative layer that gives rise to cerebellar granule cell neurons. Extensive EGL proliferation characterises the foliated structure of amniote cerebella, but the factors that regulate EGL formation, amplification within it, and differentiation from it, are incompletely understood. Here, we characterise bone morphogenic protein (BMP) signalling during cerebellar development in chick and human and show that while in chick BMP signalling correlates with external granule layer formation, in humans BMP signalling is maintained throughout the external granule layer after the onset of foliation. We also show via Immunohistochemical labelling of phosphorylated Smad1/5/9 the comparative spatiotemporal activity of BMP signalling in chick and human. Using in-ovo electroporation in chick, we demonstrate that BMP signalling is necessary for subpial migration of granule cell precursors and hence the formation of the external granule layer (EGL) prior to transit amplification. However, altering BMP signalling does not block the formation of mature granule neurons but significantly disrupts that pattern of morphological transitions that accompany transit amplification. Our results elucidate two key, temporally distinct roles for BMP signalling in vivo in organising first the assembly of the EGL from the rhombic lip and subsequently the tempo of granule neuron production within the EGL.

中文翻译：

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BMP 信号传导有助于发育中的雏鸡和人类小脑的转运放大。


外颗粒层（EGL）是短暂的增殖层，产生小脑颗粒细胞神经元。广泛的 EGL 增殖是羊膜小脑叶状结构的特征，但调节 EGL 形成、其内扩增及其分化的因素尚不完全清楚。在这里，我们表征了小鸡和人类小脑发育过程中的骨形态发生蛋白（BMP）信号传导，并表明，虽然小鸡中的BMP信号传导与外部颗粒层的形成相关，但在人类中，BMP信号传导在叶子形成后在整个外部颗粒层中得以维持。我们还通过磷酸化 Smad1/5/9 的免疫组织化学标记显示了鸡和人 BMP 信号传导的时空活性比较。在小鸡中使用卵内电穿孔，我们证明 BMP 信号传导对于颗粒细胞前体的软膜下迁移以及因此在转运扩增之前形成外部颗粒层 (EGL) 是必需的。然而，改变 BMP 信号传导不会阻止成熟颗粒神经元的形成，但会显着破坏伴随转运放大的形态转变模式。我们的结果阐明了体内 BMP 信号在组织 EGL 从菱形唇的组装以及随后 EGL 内颗粒神经元产生的节奏中的两个关键的、时间上不同的作用。