Proteomics

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Myc and the Tip60 chromatin remodeling complex control neuroblast maintenance and polarity in Drosophila


ABSTRACT: Stem cells establish cortical polarity and divide asymmetrically to simultaneously maintain themselves and generate differentiating offspring cells. Several chromatin modifiers have been identified as stemness factors in mammalian pluripotent stem cells, but whether these factors control stem cell polarity and asymmetric division has not been investigated so far. We addressed this question in Drosophila neural stem cells called neuroblasts. We identified the Tip60 chromatin remodeling complex and its interaction partner Myc to regulate target genes required for neuroblast maintenance. Knockdown of members of this complex results in loss of cortical polarity, symmetric neuroblast division and premature differentiation through nuclear entry of the transcription factor Prospero. We found that aPKC is the key target gene of Myc and the Tip60 complex subunit Domino regulating neuroblast polarity. Our transcriptome analysis further showed that Domino regulates the expression of mitotic spindle genes which were identified before as direct Myc targets. Our findings reveal an evolutionarily conserved functional link between Myc, the Tip60 complex and the molecular network controlling cell polarity and asymmetric cell division.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Drosophila Melanogaster (fruit Fly)

SUBMITTER: Christian Frese  

LAB HEAD: Andreas Wodarz

PROVIDER: PXD009939 | Pride | 2018-07-06

REPOSITORIES: Pride

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Publications

Myc and the Tip60 chromatin remodeling complex control neuroblast maintenance and polarity in <i>Drosophila</i>.

Rust Katja K   Tiwari Manu D MD   Mishra Vivek Kumar VK   Grawe Ferdi F   Wodarz Andreas A  

The EMBO journal 20180711 16


Stem cells establish cortical polarity and divide asymmetrically to simultaneously maintain themselves and generate differentiating offspring cells. Several chromatin modifiers have been identified as stemness factors in mammalian pluripotent stem cells, but whether these factors control stem cell polarity and asymmetric division has not been investigated so far. We addressed this question in <i>Drosophila</i> neural stem cells called neuroblasts. We identified the Tip60 chromatin remodeling com  ...[more]

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