Pax6 controls centriole maturation in cortical progenitors through Odf2

Marco A Tylkowski; Kefei Yang; Sigrid Hoyer-Fender; Anastassia Stoykova

doi:10.1007/s00018-014-1766-1

Pax6 controls centriole maturation in cortical progenitors through Odf2

Cell Mol Life Sci. 2015 May;72(9):1795-809. doi: 10.1007/s00018-014-1766-1. Epub 2014 Oct 29.

Authors

Marco A Tylkowski¹, Kefei Yang, Sigrid Hoyer-Fender, Anastassia Stoykova

Affiliation

¹ Research Group of Molecular Developmental Neurobiology, Department Molecular Cell Biology, Max-Planck Institute for Biophysical Chemistry, Am Faßberg 11, 37077, Göttingen, Germany.

PMID: 25352170
DOI: 10.1007/s00018-014-1766-1

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Base Sequence
Centrioles / metabolism*
Centrioles / ultrastructure
Cerebral Cortex / cytology*
Cerebral Cortex / embryology*
Eye Proteins / analysis
Eye Proteins / genetics
Eye Proteins / metabolism*
Female
Gene Expression Regulation, Developmental
HEK293 Cells
Heat-Shock Proteins / analysis
Heat-Shock Proteins / genetics
Heat-Shock Proteins / metabolism*
Homeodomain Proteins / analysis
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Humans
Male
Mice
Mice, Inbred C57BL
Molecular Sequence Data
NIH 3T3 Cells
PAX6 Transcription Factor
Paired Box Transcription Factors / analysis
Paired Box Transcription Factors / genetics
Paired Box Transcription Factors / metabolism*
Promoter Regions, Genetic
Repressor Proteins / analysis
Repressor Proteins / genetics
Repressor Proteins / metabolism*

Substances

Eye Proteins
Heat-Shock Proteins
Homeodomain Proteins
Odf2 protein, mouse
PAX6 Transcription Factor
PAX6 protein, human
Paired Box Transcription Factors
Pax6 protein, mouse
Repressor Proteins