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

• Published in: The EMBO journal Vol. 37; no. 16
• Main Authors: Rust, Katja, Tiwari, Manu D, Mishra, Vivek Kumar, Grawe, Ferdi, Wodarz, Andreas
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.08.2018; Blackwell Publishing Ltd; John Wiley and Sons Inc
• Subjects: Animals; asymmetric cell division; Asymmetric Cell Division - physiology; Asymmetry; Cell division; Cell Polarity - physiology; Cell self-renewal; Chromatin remodeling; Cortex; Differentiation; Drosophila; Drosophila melanogaster; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; EMBO05; EMBO09; EMBO39; Gene expression; Genes; Histone Acetyltransferases - genetics; Histone Acetyltransferases - metabolism; Insects; Maintenance; Myc protein; Neural stem cells; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; neuroblast; Neuroblasts; Offspring; Pluripotency; Polarity; Prospero protein; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Regulators; Spindle Apparatus - genetics; Spindle Apparatus - metabolism; stem cell; Stem cells; Target recognition; Transcription Factors - genetics; Transcription Factors - metabolism; chromatin remodeling; asymmetric cell division; neuroblast; stem cell; polarity
• ISSN: 0261-4189; 1460-2075
• DOI: 10.15252/embj.201798659

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 as regulators of genes required for neuroblast maintenance. Knockdown of Tip60 complex members 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 in regulating neuroblast polarity. Our transcriptome analysis further showed that Domino regulates the expression of mitotic spindle genes previously identified 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. Synopsis Self‐renewal of stem cells requires the establishment of cortical polarity and asymmetric cell division. Myc and the Tip60 complex control Drosophila neural stem cell maintenance, partly through regulation of polarity regulator aPKC and partly by ensuring proper asymmetric cell division and prevention of premature differentiation. Myc and the Tip60 complex interact to control neuroblast polarity and maintenance. aPKC is a common target gene of Myc and the Tip60 complex required for neuroblast polarity. Myc and the Tip60 complex are required to prevent premature neuroblast differentiation. Myc and the Tip60 complex control neuroblast spindle organization. Graphical Abstract A targeted RNAi screen reveals a role for the chromatin remodeling Tip60 complex in neural stem cell polarity and asymmetric cell division, and identifies polarity regulator aPKC as a new Myc target.