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BAF155 regulates the genesis of basal progenitors through both Pax6-dependent and independent mechanisms during cerebral cortex development

Role of BAF155 and PAX6 in cortical development

Ramanathan Narayanan
Doctoral thesis
Date of Examination: 2017-07-28
Date of issue: 2018-04-10
Advisor: Staiger, Jochen Prof. Dr.
Referee: Fischer, André Prof. Dr.
Referee: Nave, Klaus-Armin Prof. Dr.

Persistent Address: http://hdl.handle.net/11858/00-1735-0000-002E-E3B3-8

 

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Abstract

English

During mammalian development, the balance between symmetric and asymmetric division of radial glial (RG) progenitors regulates the tangential size versus radial growth of the cerebral cortex. The pool of basal progenitors (BPs) that contribute to radial growth have expanded greatly during evolution and studies in the past have identified several underlying key transcriptional and signalling mechanisms. In this study, we found that the interaction between BAF155 subunit of the mSWI/SNF chromatin-remodeling complex and Pax6, a key transcriptional regulator of corticogenesis, controls the fate choice of mouse RG specifically during early cortical development. Besides a cell-autonomous role in regulating RG division, we also found that the loss of BAF155 and Pax6 causes delamination of RG from the VZ to generate basal RG, through a novel CEP4 dependent non cell-autonomous mechanism. Interestingly, our results also suggested that such a non cell-autonomous mechanism of BP genesis might be a hallmark of primate cortical development.
Keywords: Cortical development; Basal progenitors; BAF155; PAX6; Chromatin remodeling
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