BMC Biology | |
A novel reporter of notch signalling indicates regulated and random notch activation during vertebrate neurogenesis | |
Research Article | |
Jason R Swedlow1  Kate G Storey1  Rita Fior2  Filipe Vilas-Boas3  Domingos Henrique3  | |
[1] Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dow Street, DD1 5EH, Dundee, UK;Instituto de Medicina Molecular and Instituto de Histologia e Biologia do Desenvolvimento, Faculdade de Medicina da Universidade de Lisboa, Av Prof. Egas Moniz, 1649-028, Lisboa, Portugal;Instituto de Medicina Molecular and Instituto de Histologia e Biologia do Desenvolvimento, Faculdade de Medicina da Universidade de Lisboa, Av Prof. Egas Moniz, 1649-028, Lisboa, Portugal;Champalimaud Neuroscience Programme at Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156, Oeiras, Portugal; | |
关键词: Neural Tube; Notch Signalling; Neural Progenitor; Ventricular Zone; Notch Activity; | |
DOI : 10.1186/1741-7007-9-58 | |
received in 2011-07-26, accepted in 2011-08-31, 发布年份 2011 | |
来源: Springer | |
【 摘 要 】
BackgroundBuilding the complex vertebrate nervous system involves the regulated production of neurons and glia while maintaining a progenitor cell population. Neurogenesis starts asynchronously in different regions of the embryo and occurs over a long period of time, allowing progenitor cells to be exposed to multiple extrinsic signals that regulate the production of different cell types. Notch-mediated cell-cell signalling is one of the mechanisms that maintain the progenitor pool, however, little is known about how the timing of Notch activation is related to the cell cycle and the distinct modes of cell division that generate neurons. An essential tool with which to investigate the role of Notch signalling on cell by cell basis is the development a faithful reporter of Notch activity.ResultsHere we present a novel reporter for Notch activity based on the promoter of the well characterised Notch target chick Hes5-1, coupled with multiple elements that confer instability, including a destabilized nuclear Venus fluorescent protein and the 3' untranslated region (UTR) of Hes5-1. We demonstrate that this reporter faithfully recapitulates the endogenous expression of Hes5-1 and that it robustly responds to Notch activation in the chick neural tube. Analysis of the patterns of Notch activity revealed by this reporter indicates that although Notch is most frequently activated prior to mitosis it can be activated at any time within the cell cycle. Notch active progenitors undergoing mitosis generate two daughters that both continue to experience Notch signalling. However, cells lacking Notch activity before and during mitosis generate daughters with dissimilar Notch activity profiles.ConclusionsA novel Notch reporter with multiple destabilisation elements provides a faithful read-out of endogenous Notch activity on a cell-by-cell basis, as neural progenitors progress through the cell cycle in the chick neural tube. Notch activity patterns in this cell population provide evidence for distinct Notch signalling dynamics underlying different cell division modes and for the involvement of random initiation of Notch signalling within the neuroepithelium. These findings highlight the importance of single-cell analysis in the study of the complexity of Notch activity and provide new insights into the mechanisms underlying cell fate decisions in neural progenitors.
【 授权许可】
Unknown
© Vilas-Boas et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
【 预 览 】
Files | Size | Format | View |
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RO202311108612195ZK.pdf | 5268KB | download |
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