Cerebellar granule cell migration and folia development requires Mllt11/Af1q

Abstract

ABSTRACTThe 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 the cerebellum, a structure exhibiting a distinct 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, we report a role for a microtubule-interacting protein Mllt11/Af1q (Myeloid/lymphoid or mixed-lineage leukemia; translocated to chromosome 11/All1 Fused Gene From Chromosome 1q) in the migration of cerebellar granule cells (GCs). We show that Mllt11 may serve a similar role in both tangential and radial migration of excitatory GCs. Loss ofMllt11led to an accumulation of GC 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 the perinatal folia cytoarchitecture, including alterations in the Bergmann glia fiber orientation and reduced infolding of the Purkinje cell plate. Taken together, the findings reported herein demonstrate a role for Mllt11 in regulating neuronal migration within the developing cerebellum, which is necessary for its proper neuroanatomical organization.