English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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.

Non-canonical Notch signaling represents an ancestral mechanism to regulate neural differentiation