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Título: | A novel function of DELTA-NOTCH signalling mediates the transition from proliferation to neurogenesis in neural progenitor cells |
Autor: | Hämmerle, Barbara CSIC; Tejedor, Francisco J. CSIC ORCID | Fecha de publicación: | 14-nov-2007 | Editor: | Public Library of Science | Citación: | PLoS ONE 2(11): e1169 (2007) | Resumen: | A complete account of the whole developmental process of neurogenesis involves understanding a number of complex underlying molecular processes. Among them, those that govern the crucial transition from proliferative (self-replicating) to neurogenic neural progenitor (NP) cells remain largely unknown. Due to its sequential rostro-caudal gradients of proliferation and neurogenesis, the prospective spinal cord of the chick embryo is a good experimental system to study this issue. We report that the NOTCH ligand DELTA-1 is expressed in scattered cycling NP cells in the prospective chick spinal cord preceding the onset of neurogenesis. These Delta-1-expressing progenitors are placed in between the proliferating caudal neural plate (stem zone) and the rostral neurogenic zone (NZ) where neurons are born. Thus, these Delta-1-expressing progenitors define a proliferation to neurogenesis transition zone (PNTZ). Gain and loss of function experiments carried by electroporation demonstrate that the expression of Delta-1 in individual progenitors of the PNTZ is necessary and sufficient to induce neuronal generation. The activation of NOTCH signalling by DELTA-1 in the adjacent progenitors inhibits neurogenesis and is required to maintain proliferation. However, rather than inducing cell cycle exit and neuronal differentiation by a typical lateral inhibition mechanism as in the NZ, DELTA-1/NOTCH signalling functions in a distinct manner in the PNTZ. Thus, the inhibition of NOTCH signalling arrests proliferation but it is not sufficient to elicit neuronal differentiation. Moreover, after the expression of Delta-1 PNTZ NP continue cycling and induce the expression of Tis21, a gene that is upregulated in neurogenic progenitors, before generating neurons. Together, these experiments unravel a novel function of DELTA–NOTCH signalling that regulates the transition from proliferation to neurogenesis in NP cells. We hypothesize that this novel function is evolutionary conserved. | Descripción: | 15 pages, 9 figures.-- PMID: 18000541 [PubMed].-- PMCID: PMC2064965. Supporting information (Suppl. figures S1-S3) available at: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0001169#s5 |
Versión del editor: | http://dx.doi.org/10.1371/journal.pone.0001169 | URI: | http://hdl.handle.net/10261/11907 | DOI: | 10.1371/journal.pone.0001169 | ISSN: | 1932-6203 |
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Fichero | Descripción | Tamaño | Formato | |
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Hämmerle_Tejedor_PLoS_ONE_2_11_2007.pdf | Main text file | 1,05 MB | Adobe PDF | Visualizar/Abrir |
journal.pone.0001169.s001.pdf | Fig. S1 | 125,5 kB | Adobe PDF | Visualizar/Abrir |
journal.pone.0001169.s002.pdf | Fig. S2 | 69,77 kB | Adobe PDF | Visualizar/Abrir |
journal.pone.0001169.s003.pdf | Fig. S3 | 506,96 kB | Adobe PDF | Visualizar/Abrir |
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