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The Drosophila homologue of CTIP1 (Bcl11a) and CTIP2 (Bcl11b) regulates neural stem cell temporal patterning.

Published version
Peer-reviewed

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Abstract

In the developing nervous system, neural stem cells (NSCs) use temporal patterning to generate a wide variety of different neuronal subtypes. In Drosophila, the temporal transcription factors, Hunchback, Kruppel, Pdm and Castor, are sequentially expressed by NSCs to regulate temporal identity during neurogenesis. Here, we identify a new temporal transcription factor that regulates the transition from the Pdm to Castor temporal windows. This factor, which we call Chronophage (or 'time-eater'), is homologous to mammalian CTIP1 (Bcl11a) and CTIP2 (Bcl11b). We show that Chronophage binds upstream of the castor gene and regulates its expression. Consistent with Chronophage promoting a temporal switch, chronophage mutants generate an excess of Pdm-specified neurons and are delayed in generating neurons associated with the Castor temporal window. In addition to promoting the Pdm to Castor transition, Chronophage also represses the production of neurons generated during the earlier Hunchback and Kruppel temporal windows. Genetic interactions with Hunchback and Kruppel indicate that Chronophage regulates NSC competence to generate Hunchback- and Kruppel-specified neurons. Taken together, our results suggest that Chronophage has a conserved role in temporal patterning and neuronal subtype specification.

Description

Funder: European Molecular Biology Organization; Id: http://dx.doi.org/10.13039/100004410


Funder: University of Cambridge; Id: http://dx.doi.org/10.13039/501100000735

Keywords

Bcl11a, Bcl11b, CTIP1/2, Chronophage, Neural development, Neural stem cells, Temporal patterning, Animals, DNA-Binding Proteins, Drosophila, Drosophila Proteins, Mammals, Neural Stem Cells, Receptors, Cell Surface, Transcription Factors, Tumor Suppressor Proteins

Journal Title

Development

Conference Name

Journal ISSN

0950-1991
1477-9129

Volume Title

Publisher

The Company of Biologists
Sponsorship
Wellcome Trust (092545/Z/10/Z)
Wellcome Trust (103792/Z/14/Z)
Royal Society (RP150061)
Royal Society (RSRP\R\210002)
Wellcome Trust (203798/Z/16/Z)
Cancer Research Uk (None)
Wellcome Trust (203144/Z/16/Z)