TLX3 Regulates CGN Progenitor Proliferation During Cerebellum Development and Its Dysfunction Can Lead to Autism

Overview

Journal iScience

Publisher Cell Press

Date 2024 Dec 4

PMID 39628587

Authors

Surendran Parvathy

Budhaditya Basu

Suresh Surya

Rahul Jose

Vadakkath Meera

Paul Ann Riya

Nair Pradeep Jyothi

Rajendran Sanalkumar

Viviane Praz

Nicolo Riggi

Biju Surendran Nair

Kamalesh K Gulia

Mukesh Kumar

Balachandran Krishnamma Binukumar

Jackson James

Affiliations

Soon will be listed here.

Abstract

, 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 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 presence of variants with uncharacterized mutations in human cases of autism spectrum disorder (ASD). Altogether, our study establishes as a critical gene involved in developing GNPs and that its deletion from the early developmental stage culminates in autism.

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