
BMP 신호 전달은 소뇌 과립 세포 전구체의 피질 아래 이동을 위해 필요하며, 과립 세포 성숙의 속도를 조절한다.


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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.

Significance statement Improper development of cerebellar granule neurons can manifest in a plethora of neurodevelopmental disorders, including but not limited to medulloblastoma and autism. Many studies have sought to understand the role of developmental signalling pathways in granule cell neurogenesis, using genetic manipulation in transgenic mice. To complement these insights, we have used comparative assessment of BMP signalling during development in chick and human embryos and in vivo manipulation of the chick to understand and segregate the spatiotemporal roles of BMP signalling, yielding important insights on evolution and in consideration of future therapeutic avenues that target BMP signalling.

### Competing Interest Statement

The authors have declared no competing interest.

BMP signalling facilitates transit amplification in the developing chick and human cerebellum

발달-과정에서-bmp-신호-전달이-소뇌-과립-세포-신경-생성을-위한-전이-증폭을-촉진한다-


발달 과정에서 BMP 신호 전달이 소뇌 과립 세포 신경 생성을 위한 전이 증폭을 촉진한다.
