A ROLE FOR MLLT11 IN THE DEVELOPMENT OF RETINAL AND CEREBELLAR CYTOARCHITECTURE

Abstract

The organization of neurons into distinct layers, known as lamination, is a common feature of the nervous system. This process, which arises from the direct coupling of neurogenesis and neuronal migration, plays a crucial role in the development of both the retina and the cerebellum. These structures exhibit a distinct and characteristic cytoarchitecture, with cells arranged in discrete layers. Disruptions to neuronal migration and lamination can lead to various neurodevelopmental disorders, highlighting the significance of understanding their underlying regulators. Here, I report a role for a microtubule-interacting protein, Mllt11 (Myeloid/lymphoid or mixed-lineage leukemia; translocated to chromosome 11/All1 Fused Gene From Chromosome 1q), in the migration of retinal and cerebellar neurons, contributing to the laminated organization of their respective structures. In the retina, I show that Mllt11 is involved in the proper formation of the ganglion cell layer. Loss of Mllt11 leads to impaired migration of retinal ganglion cells and displaced amacrine cells, resulting in their ectopic accumulation closer to their birthplace. In the cerebellum, I show that Mllt11 may serve a similar role in both tangential and radial migration of excitatory granule cells (GCs). Loss of Mllt11 led to an accumulation of granule cell precursors in the rhombic lip region and a reduction in the number of GCs successfully populating developing folia. Consequently, this results in smaller folia and an overall reduction in cerebellar size. Furthermore, analysis of the anchoring centres, reveals disruptions in cytoarchitecture, including alterations in the Bergmann glia fiber orientation and reduced infolding of the Purkinje cell plate. Taken together, the findings reported herein demonstrate the critical role of Mllt11 in regulating neuronal migration in both the retina and cerebellum, which is necessary for their proper lamination.