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Exploring the Roles of Bmp Signalling During the Development of Rhombic Lip Progenitors in the Avian Cerebellum
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Exploring the Roles of Bmp Signalling During the Development of Rhombic Lip Progenitors in the Avian Cerebellum
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Dissertation
Exploring the Roles of Bmp Signalling During the Development of Rhombic Lip Progenitors in the Avian Cerebellum
2020
Overview
Cerebellar granule cell precursors (GCP) are the most abundant neuronal progenitor population in the brain, which, given the structural simplicity of the cerebellum make them a good model for investigating mechanisms regulating neurogenesis. GCPs are born at the rhombic lip; the germinal zone of glutamatergic neurons in the cerebellar anlage from E6 in the chick. From the rhombic lip GCPs undergo subpial, tangential migration to form a transiently proliferative layer; the external granule layer (EGL), followed by inward radial migration towards the inner granule cell layer (IGL) once they have undergone neurogenic differentiation. GCPs undergo massive proliferation within the EGL, influenced by Sonic Hedgehog (SHH) from underlying Purkinje neurons, however triggers for termination of GCP proliferation are poorly understood. Through spatiotemporal characterisation and in ovo targeted genetic dysregulation of the bone morphogenetic protein (BMP) signalling pathway, a known inhibitor of SHH, in the embryonic chicken hindbrain, I have shown similarities in expression of BMP activity between chick and human cerebellar development and suggest a novel role for BMP signalling during GCP development in the chick. In vivo experimental data shows that inhibition of BMP signalling affects the recruitment to and subpial migration of granule cell precursors along the EGL, however not their specification. GCPs can be recruited to the EGL following upregulation of BMP signalling, however, following the onset of SHH signalling at E8 GCPs in the EGL exit the cell cycle, differentiate, and radially migrate inwards along the Bergmann glia fibres, which are shown here to mature at E8 in the chick. This novel role is temporally intermediate to those previously described during early rhombic lip specification and later in the induction of differentiation and suggest that BMP signalling is involved in regulating the migration of granule cells from their specification at the rhombic lip to their final destination in the granule cell layer.
Publisher
ProQuest Dissertations & Theses
Subject
