title: Regulation of Tlx3 by Pax6 is required for the restricted expression of Chrnα3 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-α3 subunit (Chrnα3) 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).
authors.affiliation: Neuro Stem Cell Biology Laboratory, Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala-695 014, India.
authors.forename: Thulasi Sheela
authors.initials: TS
authors.lastname: Divya
authors.affiliation: Neuro Stem Cell Biology Laboratory, Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala-695 014, India.
authors.forename: Soundararajan
authors.initials: S
authors.lastname: Lalitha
authors.affiliation: Neuro Stem Cell Biology Laboratory, Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala-695 014, India.
authors.forename: Surendran
authors.initials: S
authors.lastname: Parvathy
authors.affiliation: Neuro Stem Cell Biology Laboratory, Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala-695 014, India.
authors.forename: Chandramohan
authors.initials: C
authors.lastname: Subashini
authors.affiliation: Neuro Stem Cell Biology Laboratory, Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala-695 014, India.
authors.forename: Rajendran
authors.initials: R
authors.lastname: Sanalkumar
authors.affiliation: Neuro Stem Cell Biology Laboratory, Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala-695 014, India.
authors.forename: Sivadasan Bindu
authors.initials: SB
authors.lastname: Dhanesh
authors.affiliation: Neuro Stem Cell Biology Laboratory, Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala-695 014, India.
authors.forename: Vazhanthodi Abdul
authors.initials: VA
authors.lastname: Rasheed
authors.affiliation: Neuro Stem Cell Biology Laboratory, Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala-695 014, India.
authors.forename: Mundackal Sivaraman
authors.initials: MS
authors.lastname: Divya
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai-400005, India.
authors.forename: Shubha
authors.initials: S
authors.lastname: Tole
authors.affiliation: Neuro Stem Cell Biology Laboratory, Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala-695 014, India.
authors.forename: Jackson
authors.initials: J
authors.lastname: James
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D016000:Cluster Analysis; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D000071841:PAX6 Transcription Factor / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics*; D013116:Spinal Cord
chemical_list: D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D011978:Receptors, Nicotinic; C487377:Tlx3 protein, mouse