Geminin Orchestrates Somite Formation by Regulating Fgf8 and Notch Signaling

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.

Light microscopy‐based elastography for the mechanical characterization of zebrafish somitogenesis

“…The appearance of morphologically distinct somites is driven by the tightly regulated MET of cells in the presomitic mesoderm during the formation of new somite boundaries [13]. The formation of somites and their derivatives is fundamental to vertebrate animals including humans, and zebrafish somitogenesis has thus been a powerful model for both basic developmental biology studies [14,15] as well as the investigation of human diseases such as muscular dystrophy [16][17][18][19]. Here, we extend the utility of this system to investigate changes in tissue mechanical stiffness during MET in vivo.…”