Cerebellar granule cell migration and folia development require Mllt11/Af1q/Tcf7c.

Area of Science:

• Neuroscience
• Developmental Biology
• Cell Biology

Background:

• Neuronal lamination, the organization of neurons into layers, is fundamental to nervous system development.
• This process involves neurogenesis and neuronal migration, particularly critical in the cerebellum's layered structure.
• Disruptions in neuronal migration are linked to neurodevelopmental disorders, underscoring the need to understand its molecular regulation.

Purpose of the Study:

• To investigate the role of Mllt11 (myeloid/lymphoid or mixed-lineage leukemia; translocated to chromosome 11) in cerebellar granule cell (GC) migration.
• To elucidate the molecular mechanisms by which Mllt11 influences GC migration and cerebellar development.

Main Methods:

• Genetic manipulation to study the loss of Mllt11 function in cerebellar development.
• Analysis of GC precursor accumulation, migration patterns, and cerebellar cytoarchitecture.
• Investigation of Mllt11 interactions with non-muscle myosin IIB (NMIIB).

Main Results:

• Loss of Mllt11 resulted in GC precursor accumulation and reduced GC migration into developing folia.
• Mllt11 deficiency led to smaller folia and overall reduced cerebellar size.
• Disruptions in perinatal folia cytoarchitecture, including altered Bergmann glia and Purkinje cell plate infolding, were observed.
• Mllt11 interacts with NMIIB, and its loss reduces NMIIB expression, suggesting a role in regulating GC migration.

Conclusions:

• Mllt11 plays a significant role in both tangential and radial migration of cerebellar granule cells.
• Mllt11 is essential for the proper neuroanatomical organization of the developing cerebellum.
• The interaction between Mllt11 and NMIIB is a key mechanism underlying Mllt11's function in neuronal migration.