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Anterior-Posterior Gradient in Neural Stem and Daughter Cell Proliferation Governed by Spatial and Temporal Hox Control
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0001-5095-541X
2017 (English)In: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 27, no 8, 1161-1172 p.Article in journal (Refereed) Published
Abstract [en]

A readily evident feature of animal central nervous systems (CNSs), apparent in all vertebrates and many invertebrates alike, is its "wedge-like appearance, with more cells generated in anterior than posterior regions. This wedge could conceivably be established by an antero-posterior (A-P) gradient in the number of neural progenitor cells, their proliferation behaviors, and/or programmed cell death (PCD). However, the contribution of each of these mechanisms, and the underlying genetic programs, are not well understood. Building upon recent progress in the Drosophila melanogaster (Drosophila) ventral nerve cord (VNC), we address these issues in a comprehensive manner. We find that, although PCD plays a role in controlling cell numbers along the A-P axis, the main driver of the wedge is a gradient of daughter proliferation, with divisions directly generating neurons (type 0) being more prevalent posteriorly and dividing daughters (type I) more prevalent anteriorly. In addition, neural progenitor (NB) cell-cycle exit occurs earlier posteriorly. The gradient of type I amp;gt; 0 daughter proliferation switch and NB exit combine to generate radically different average lineage sizes along the A-P axis, differing by more than 3-fold in cell number. We find that the Hox homeotic genes, expressed in overlapping A-P gradients and with a late temporal onset in NBs, trigger the type I amp;gt; 0 daughter proliferation switch and NB exit. Given the highly evolutionarily conserved expression of overlapping Hox homeotic genes in the CNS, our results point to a common mechanism for generating the CNS wedge.

Place, publisher, year, edition, pages
CELL PRESS , 2017. Vol. 27, no 8, 1161-1172 p.
National Category
Developmental Biology
Identifiers
URN: urn:nbn:se:liu:diva-137604DOI: 10.1016/j.cub.2017.03.023ISI: 000399986500023PubMedID: 28392108OAI: oai:DiVA.org:liu-137604DiVA: diva2:1097367
Note

Funding Agencies|Swedish Research Council [621-2013-5258]; Knut and Alice Wallenberg Foundation [KAW2011.0165, KAW2012.0101]; Swedish Cancer Foundation [150663]

Available from: 2017-05-22 Created: 2017-05-22 Last updated: 2017-05-22

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