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Regulation of Tlx3 by Pax6 is required for the restricted expression of Chrn?3 in Cerebellar Granule Neuron progenitors during development.


ABSTRACT: Homeobox gene Tlx3 is known to promote glutamatergic differentiation and is expressed in post-mitotic neurons of CNS. Contrary to this here, we discovered that Tlx3 is expressed in the proliferating progenitors of the external granule layer in the cerebellum, and examined factors that regulate this expression. Using Pax6(-/-)Sey mouse model and molecular interaction studies we demonstrate Pax6 is a key activator of Tlx3 specifically in cerebellum, and induces its expression starting at embryonic day (E)15. By Postnatal day (PN)7, Tlx3 is expressed in a highly restricted manner in the cerebellar granule neurons of the posterior cerebellar lobes, where it is required for the restricted expression of nicotinic cholinergic receptor-?3 subunit (Chrn?3) and other genes involved in formation of synaptic connections and neuronal migration. These results demonstrate a novel role for Tlx3 and indicate that Pax6-Tlx3 expression and interaction is part of a region specific regulatory network in cerebellum and its deregulation during development could possibly lead to Autistic spectral disorders (ASD).

SUBMITTER: Divya TS 

PROVIDER: S-EPMC4959012 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Regulation of Tlx3 by Pax6 is required for the restricted expression of Chrnα3 in Cerebellar Granule Neuron progenitors during development.

Divya Thulasi Sheela TS   Lalitha Soundararajan S   Parvathy Surendran S   Subashini Chandramohan C   Sanalkumar Rajendran R   Dhanesh Sivadasan Bindu SB   Rasheed Vazhanthodi Abdul VA   Divya Mundackal Sivaraman MS   Tole Shubha S   James Jackson J  

Scientific reports 20160725


Homeobox gene Tlx3 is known to promote glutamatergic differentiation and is expressed in post-mitotic neurons of CNS. Contrary to this here, we discovered that Tlx3 is expressed in the proliferating progenitors of the external granule layer in the cerebellum, and examined factors that regulate this expression. Using Pax6(-/-)Sey mouse model and molecular interaction studies we demonstrate Pax6 is a key activator of Tlx3 specifically in cerebellum, and induces its expression starting at embryonic  ...[more]

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