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Developmental Biology
Article
License: Elsevier Non-Commercial
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Developmental Biology
Article . 2009
License: Elsevier Non-Commercial
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Developmental Biology
Article . 2009 . Peer-reviewed
License: Elsevier Non-Commercial
Data sources: Crossref
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Dll1 and Dll4 function sequentially in the retina and pV2 domain of the spinal cord to regulate neurogenesis and create cell diversity

Authors: Achim Gossler; Susana S. Lopes; Susana Ferreira Rocha; Domingos Henrique; Domingos Henrique;

Dll1 and Dll4 function sequentially in the retina and pV2 domain of the spinal cord to regulate neurogenesis and create cell diversity

Abstract

Signalling mediated by Notch receptors is known to have multiple functions during vertebrate neural development, regulating processes like progenitor differentiation and cell type diversification. Various Notch ligands are expressed in the developing nervous system and their activities might contribute to this multiplicity of functions. Here, we show that two Delta-like genes, Dll1 and Dll4, are sequentially expressed in differentiating neurons of the embryonic mouse retina and spinal cord's pV2 domain, with Dll1 starting to be expressed before Dll4. Analysis of Dll1 mutants reveals this gene is necessary and sufficient to maintain a pool of progenitors in the embryonic neuroepithelium. Accordingly, in the spinal cord domains where Dll1 is the only expressed Notch ligand, its inactivation leads to an increased rate of neurogenesis and premature differentiation of neural progenitors. In contrast, in the pV2 domain and retina where Dll1 is co-expressed with Dll4, progenitors are not exhausted and cell diversity is maintained. Together, our results support a model where Dll1 and Dll4 are part of a unique genetic circuitry that regulates subsequent steps of neurogenesis in the retina and pV2 domain: while Dll1 serves to prevent the untimely differentiation of neural progenitors, Dll4 might function to generate diversity within the population of differentiating neurons.

Keywords

Heterozygote, Neurogenesis, Cell fate diversity, Delta ligands, Models, Biological, Retina, Mice, Animals, Molecular Biology, Notch signaling, Alleles, Crosses, Genetic, In Situ Hybridization, Adaptor Proteins, Signal Transducing, Mice, Knockout, Spinal cord, Calcium-Binding Proteins, Homozygote, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Cell Biology, Embryo, Mammalian, Immunohistochemistry, Mice, Mutant Strains, Spinal Cord, Intercellular Signaling Peptides and Proteins, Developmental Biology

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
59
Top 10%
Top 10%
Top 10%
hybrid