TLX3 regulates CGN progenitor proliferation during cerebellum development and its dysfunction can lead to autism.

ABSTRACT: Tlx3, a master regulator of the fate specification of excitatory neurons, is primarily known to function in post-mitotic cells. Although we have previously identified TLX3 expression in the proliferating granule neuron progenitors (GNPs) of cerebellum, its primary role is unknown. Here, we demonstrate that the dysfunction of Tlx3 from the GNPs significantly reduced its proliferation through regulating anti-proliferative genes. Consequently, the altered generation of GNPs resulted in cerebellar hypoplasia, patterning defects, granule neuron-Purkinje ratio imbalance, and aberrant synaptic connections in the cerebellum. This altered cerebellar homeostasis manifested into a typical autism-like behavior in mice with motor, and social function disabilities. We also show the presenc

SUBMITTER: Parvathy S 

PROVIDER: S-EPMC11612787 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature