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Geminin Orchestrates Somite Formation by Regulating Fgf8 and Notch Signaling

During somitogenesis, Fgf8 maintains the predifferentiation stage of presomitic mesoderm (PSM) cells and its retraction gives a cue for somite formation. Delta/Notch initiates the expression of oscillation genes in the tail bud and subsequently contributes to somite formation in a periodic way. Whet...

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Detalles Bibliográficos
Autores principales: Huang, Wei, Zhang, Yu, Cao, Kang, Luo, Lingfei, Huang, Sizhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6011172/
https://www.ncbi.nlm.nih.gov/pubmed/29984243
http://dx.doi.org/10.1155/2018/6543196
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author Huang, Wei
Zhang, Yu
Cao, Kang
Luo, Lingfei
Huang, Sizhou
author_facet Huang, Wei
Zhang, Yu
Cao, Kang
Luo, Lingfei
Huang, Sizhou
author_sort Huang, Wei
collection PubMed
description During somitogenesis, Fgf8 maintains the predifferentiation stage of presomitic mesoderm (PSM) cells and its retraction gives a cue for somite formation. Delta/Notch initiates the expression of oscillation genes in the tail bud and subsequently contributes to somite formation in a periodic way. Whether there exists a critical factor coordinating Fgf8 and Notch signaling pathways is largely unknown. Here, we demonstrate that the loss of function of geminin gave rise to narrower somites as a result of derepressed Fgf8 gradient in the PSM and tail bud. Furthermore, in geminin morphants, the somite boundary could not form properly but the oscillation of cyclic genes was normal, displaying the blurry somitic boundary and disturbed somite polarity along the AP axis. In mechanism, these manifestations were mediated by the disrupted association of the geminin/Brg1 complex with intron 3 of mib1. The latter interaction was found to positively regulate mib1 transcription, Notch activity, and sequential somite segmentation during somitogenesis. In addition, geminin was also shown to regulate the expression of deltaD in mib1-independent way. Collectively, our data for the first time demonstrate that geminin regulates Fgf8 and Notch signaling to regulate somite segmentation during somitogenesis.
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spelling pubmed-60111722018-07-08 Geminin Orchestrates Somite Formation by Regulating Fgf8 and Notch Signaling Huang, Wei Zhang, Yu Cao, Kang Luo, Lingfei Huang, Sizhou Biomed Res Int Research Article During somitogenesis, Fgf8 maintains the predifferentiation stage of presomitic mesoderm (PSM) cells and its retraction gives a cue for somite formation. Delta/Notch initiates the expression of oscillation genes in the tail bud and subsequently contributes to somite formation in a periodic way. Whether there exists a critical factor coordinating Fgf8 and Notch signaling pathways is largely unknown. Here, we demonstrate that the loss of function of geminin gave rise to narrower somites as a result of derepressed Fgf8 gradient in the PSM and tail bud. Furthermore, in geminin morphants, the somite boundary could not form properly but the oscillation of cyclic genes was normal, displaying the blurry somitic boundary and disturbed somite polarity along the AP axis. In mechanism, these manifestations were mediated by the disrupted association of the geminin/Brg1 complex with intron 3 of mib1. The latter interaction was found to positively regulate mib1 transcription, Notch activity, and sequential somite segmentation during somitogenesis. In addition, geminin was also shown to regulate the expression of deltaD in mib1-independent way. Collectively, our data for the first time demonstrate that geminin regulates Fgf8 and Notch signaling to regulate somite segmentation during somitogenesis. Hindawi 2018-06-07 /pmc/articles/PMC6011172/ /pubmed/29984243 http://dx.doi.org/10.1155/2018/6543196 Text en Copyright © 2018 Wei Huang et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Huang, Wei
Zhang, Yu
Cao, Kang
Luo, Lingfei
Huang, Sizhou
Geminin Orchestrates Somite Formation by Regulating Fgf8 and Notch Signaling
title Geminin Orchestrates Somite Formation by Regulating Fgf8 and Notch Signaling
title_full Geminin Orchestrates Somite Formation by Regulating Fgf8 and Notch Signaling
title_fullStr Geminin Orchestrates Somite Formation by Regulating Fgf8 and Notch Signaling
title_full_unstemmed Geminin Orchestrates Somite Formation by Regulating Fgf8 and Notch Signaling
title_short Geminin Orchestrates Somite Formation by Regulating Fgf8 and Notch Signaling
title_sort geminin orchestrates somite formation by regulating fgf8 and notch signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6011172/
https://www.ncbi.nlm.nih.gov/pubmed/29984243
http://dx.doi.org/10.1155/2018/6543196
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AT luolingfei gemininorchestratessomiteformationbyregulatingfgf8andnotchsignaling
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