title: Pax6 controls centriole maturation in cortical progenitors through Odf2.
abstract: Cortical glutamatergic neurons are generated by radial glial cells (RGCs), specified by the expression of transcription factor (TF) Pax6, in the germinative zones of the dorsal telencephalon. Here, we demonstrate that Pax6 regulates the structural assembly of the interphase centrosomes. In the cortex of the Pax6-deficient Small eye (Sey/Sey) mutant, we find a defect of the appendages of the mother centrioles, indicating incomplete centrosome maturation. Consequently, RGCs fail to generate primary cilia, and instead of staying in the germinative zone for renewal, RGCs detach from the ventricular surface thus affecting the interkinetic nuclear migration and they exit prematurely from mitosis. Mechanistically, we show that TF Pax6 directly regulates the activity of the Odf2 gene encoding for the appendage-specific protein Odf2 with a role for the assembly of mother centriole. Our findings demonstrate a molecular mechanism that explains important characteristics of the centrosome disassembly and malfunctioning in developing cortex lacking Pax6.
authors.affiliation: Research Group of Molecular Developmental Neurobiology, Department Molecular Cell Biology, Max-Planck Institute for Biophysical Chemistry, Am Faßberg 11, 37077, Göttingen, Germany.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Tylkowski
authors.forename: Kefei
authors.initials: K
authors.lastname: Yang
authors.forename: Sigrid
authors.initials: S
authors.lastname: Hoyer-Fender
authors.forename: Anastassia
authors.initials: A
authors.lastname: Stoykova
mesh_terms: D000818:Animals; D001483:Base Sequence; D002502:Centrioles / Q000378:metabolism* / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology*; D005136:Eye Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006360:Heat-Shock Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D005136:Eye Proteins; D006360:Heat-Shock Proteins; D018398:Homeodomain Proteins; C490106:Odf2 protein, mouse; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins