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Prdm1a and olig4 act downstream of Notch signaling to regulate cell fate at the neural plate border.

ABSTRACT: The zinc finger domain transcription factor prdm1a plays an integral role in the development of the neural plate border cell fates, including neural crest cells and Rohon-Beard (RB) sensory neurons. However, the mechanisms underlying prdm1a function in cell fate specification is unknown. Here, we test more directly how prdm1a functions in this cell fate decision. Rather than affecting cell death or proliferation at the neural plate border, prdm1a acts explicitly on cell fate specification by counteracting olig4 expression in the neighboring interneuron domain. olig4 expression is expanded in prdm1a mutants and olig4 knockdown can rescue the reduced or abrogated neural crest and RB neuron phenotype in prdm1a mutants, suggesting a permissive role for prdm1a in neural plate border-derived cell fates. In addition, prdm1a expression is upregulated in the absence of Notch function, and inhibiting Notch signaling fails to rescue prdm1a mutants. This suggests that prdm1a functions downstream of Notch in the regulation of cell fate at the neural plate border and that Notch regulates the total number of progenitor cells at the neural plate border.

SUBMITTER: Hernandez-Lagunas L

PROVIDER: S-EPMC3144709 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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prdm1a and olig4 act downstream of Notch signaling to regulate cell fate at the neural plate border.

Hernandez-Lagunas Laura L Powell Davalyn R DR Law Jera J Grant Kelly A KA Artinger Kristin Bruk KB

Developmental biology 20110613 2

The zinc finger domain transcription factor prdm1a plays an integral role in the development of the neural plate border cell fates, including neural crest cells and Rohon-Beard (RB) sensory neurons. However, the mechanisms underlying prdm1a function in cell fate specification is unknown. Here, we test more directly how prdm1a functions in this cell fate decision. Rather than affecting cell death or proliferation at the neural plate border, prdm1a acts explicitly on cell fate specification by cou ...[more]

PMID: 21689645

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Project description:BACKGROUND:Cellular differentiation is a critical process during development of multicellular animals that must be tightly controlled in order to avoid precocious differentiation or failed generation of differentiated cell types. Research in flies, vertebrates, and nematodes has led to the identification of a conserved role for Notch signaling as a mechanism to regulate cellular differentiation regardless of tissue/cell type. Notch signaling can occur through a canonical pathway that results in the activation of hes gene expression by a complex consisting of the Notch intracellular domain, SuH, and the Mastermind co-activator. Alternatively, Notch signaling can occur via a non-canonical mechanism that does not require SuH or activation of hes gene expression. Regardless of which mechanism is being used, high Notch activity generally inhibits further differentiation, while low Notch activity promotes differentiation. Flies, vertebrates, and nematodes are all bilaterians, and it is therefore unclear if Notch regulation of differentiation is a bilaterian innovation, or if it represents a more ancient mechanism in animals. RESULTS:To reconstruct the ancestral function of Notch signaling we investigate Notch function in a non-bilaterian animal, the sea anemone Nematostella vectensis (Cnidaria). Morpholino or pharmacological knockdown of Nvnotch causes increased expression of the neural differentiation gene NvashA. Conversely, overactivation of Notch activity resulting from overexpression of the Nvnotch intracellular domain or by overexpression of the Notch ligand Nvdelta suppresses NvashA. We also knocked down or overactivated components of the canonical Notch signaling pathway. We disrupted NvsuH with morpholino or by overexpressing a dominant negative NvsuH construct. We saw no change in expression levels for Nvhes genes or NvashA. Overexpression of Nvhes genes did not alter NvashA expression levels. Lastly, we tested additional markers associated with neuronal differentiation and observed that non-canonical Notch signaling broadly suppresses neural differentiation in Nematostella. CONCLUSIONS:We conclude that one ancestral role for Notch in metazoans was to regulate neural differentiation. Remarkably, we found no evidence for a functional canonical Notch pathway during Nematostella embryogenesis, suggesting that the non-canonical hes-independent Notch signaling mechanism may represent an ancestral Notch signaling pathway.

Dataset Information

Prdm1a and olig4 act downstream of Notch signaling to regulate cell fate at the neural plate border.

Publications

prdm1a and olig4 act downstream of Notch signaling to regulate cell fate at the neural plate border.

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