title: Regulation of Nematostella neural progenitors by SoxB, Notch and bHLH genes.
abstract: Notch signalling, SoxB and Group A bHLH 'proneural' genes are conserved regulators of the neurogenic program in many bilaterians. However, the ancestry of their functions and interactions is not well understood. We address this question in the sea anemone Nematostella vectensis, a representative of the Cnidaria, the sister clade to the Bilateria. It has previously been found that the SoxB orthologue NvSoxB(2) is expressed in neural progenitor cells (NPCs) in Nematostella and promotes the development of both neurons and nematocytes, whereas Notch signalling has been implicated in the negative regulation of neurons and the positive regulation of nematocytes. Here, we clarify the role of Notch by reporting that inhibition of Notch signalling increases the numbers of both neurons and nematocytes, as well as increasing the number of NvSoxB(2)-expressing cells. This suggests that Notch restricts neurogenesis by limiting the generation of NPCs. We then characterise NvAth-like (Atonal/Neurogenin family) as a positive regulator of neurogenesis that is co-expressed with NvSoxB(2) in a subset of dividing NPCs, while we find that NvAshA (Achaete-scute family) and NvSoxB(2) are co-expressed in non-dividing cells only. Reciprocal knockdown experiments reveal a mutual requirement for NvSoxB(2) and NvAth-like in neural differentiation; however, the primary expression of each gene is independent of the other. Together, these data demonstrate that Notch signalling and NvSoxB(2) regulate Nematostella neural progenitors via parallel yet interacting mechanisms; with different aspects of these interactions being shared with Drosophila and/or vertebrate neurogenesis.
authors.affiliation: Sars Centre for Marine Molecular Biology, University of Bergen, Thormøhlensgate 55, Bergen N-5008, Norway gsrichards18@gmail.com fabian.rentzsch@sars.uib.no.
authors.forename: Gemma Sian
authors.initials: GS
authors.lastname: Richards
authors.affiliation: Sars Centre for Marine Molecular Biology, University of Bergen, Thormøhlensgate 55, Bergen N-5008, Norway gsrichards18@gmail.com fabian.rentzsch@sars.uib.no.
authors.forename: Fabian
authors.initials: F
authors.lastname: Rentzsch
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D018929:Cell Culture Techniques; D055785:Gene Knockdown Techniques; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D051880:Receptors, Notch / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055749:SOXB2 Transcription Factors / Q000235:genetics / Q000378:metabolism; D012615:Sea Anemones / Q000166:cytology / Q000196:embryology* / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051880:Receptors, Notch; D055749:SOXB2 Transcription Factors
keywords: Cnidaria; DAPT; Neurogenesis; Proneural genes