Restriction on self-renewing asymmetric division is coupled to terminal asymmetric division in the Drosophila CNS

Autoři: Ivana Gaziova aff001;  Michael Gazi aff001;  Jordan Mar aff003;  Krishna Moorthi Bhat aff001
Působiště autorů: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, United States of America aff001;  Texas Biomedical Research Institute, Department of Virology, 8715 W. Military Dr. San Antonio, United States of America aff002;  Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, United States of America aff003
Vyšlo v časopise: Restriction on self-renewing asymmetric division is coupled to terminal asymmetric division in the Drosophila CNS. PLoS Genet 16(9): e1009011. doi:10.1371/journal.pgen.1009011
Kategorie: Research Article
doi: 10.1371/journal.pgen.1009011


Neuronal precursor cells undergo self-renewing and non-self-renewing asymmetric divisions to generate a large number of neurons of distinct identities. In Drosophila, primary precursor neuroblasts undergo a varying number of self-renewing asymmetric divisions, with one known exception, the MP2 lineage, which undergoes just one terminal asymmetric division similar to the secondary precursor cells. The mechanism and the genes that regulate the transition from self-renewing to non-self-renewing asymmetric division or the number of times a precursor divides is unknown. Here, we show that the T-box transcription factor, Midline (Mid), couples these events. We find that in mid loss of function mutants, MP2 undergoes additional self-renewing asymmetric divisions, the identity of progeny neurons generated dependent upon Numb localization in the parent MP2. MP2 expresses Mid transiently and an over-expression of mid in MP2 can block its division. The mechanism which directs the self-renewing asymmetric division of MP2 in mid involves an upregulation of Cyclin E. Our results indicate that Mid inhibits cyclin E gene expression by binding to a variant Mid-binding site in the cyclin E promoter and represses its expression without entirely abolishing it. Consistent with this, over-expression of cyclin E in MP2 causes its multiple self-renewing asymmetric division. These results reveal a Mid-regulated pathway that restricts the self-renewing asymmetric division potential of cells via inhibiting cyclin E and facilitating their exit from cell cycle.

Klíčová slova:

Cell cycle and cell division – Cyclins – Drosophila melanogaster – Gene expression – Neurons – Precursor cells – Statistical data – Cell division analysis


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