Geminin Orchestrates Somite Formation by Regulating Fgf8 and Notch Signaling.

Wei Huang,Lingfei Luo,Yu Zhang,Sizhou Huang,Kang Cao

doi:10.1155/2018/6543196

Wei Huang, Lingfei Luo + Show 3 more

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https://doi.org/10.1155/2018/6543196

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Abstract

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.

Highlights

Somitogenesis is a critical developmental event whereby pairs of epithelial spheres, named somites, form periodically from the mesenchymal presomitic mesoderm (PSM) [1]
To check whether the defective somite phenotype resulted from cell apoptosis in geminin morphants, we coinjected geminin MO (GemMO) and p53MO together [44, 55] and examined whether defective somites existed in Gem/p53 morphants
The embryos injected with GemMO and p53MO did not exhibit developmental delay but displayed disturbed somites as in geminin morphants (Figure 1(c))

Summary

Introduction

Somitogenesis is a critical developmental event whereby pairs of epithelial spheres, named somites, form periodically from the mesenchymal presomitic mesoderm (PSM) [1]. Mutants with mutations in Notch signaling-related genes displayed segmentation defects [14, 15], including disrupted somite boundary formation [14,15,16,17] and “salt and pepper” expression pattern of cycling genes such as deltaC and her1 [18, 19]. These reports suggested that tight control of Notch signaling was crucial for proper somite segmentation

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