Rhythmic Gene Expression in Somite Formation and Neural Development

Abstract

In mouse embryos, somite formation occurs every two hours, and this periodic event is regulated by a biological clock called the segmentation clock, which involves cyclic expression of the basic helix-loop-helix gene Hes7. Hes7 expression oscillates by negative feedback and is cooperatively regulated by Fgf and Notch signaling. Both loss of expression and sustained expression of Hes7 result in severe somite fusion, suggesting that Hes7 oscillation is required for proper somite segmentation. Expression of a related gene, Hes1, also oscillates by negative feedback with a period of about two hours in many cell types such as neural progenitor cells. Hes1 is required for maintenance of neural progenitor cells, but persistent Hes1 expression inhibits proliferation and differentiation of these cells, suggesting that Hes1 oscillation is required for their proper activities. Hes1 oscillation regulates cyclic expression of the proneural gene Neurogenin2 (Ngn2) and the Notch ligand Delta1, which in turn lead to maintenance of neural progenitor cells by mutual activation of Notch signaling. Taken together, these results suggest that oscillatory expression with short periods (ultradian oscillation) plays an important role in many biological events.

Interactions between VEGFR and Notch signaling pathways in endothelial and neural cells

“…These data confirm previous reports in mice of the circadian expression of VEGF-A in murine tumor cells [66]. Interestingly, Notch signaling is also regulated in an oscillatory fashion and the gene Hes7 , which is regulated by the Notch and Fgf/Mapk pathways is a crucial component of the segmentation clock [67, 68]. The Notch-VEGF-A interactions in the oscillatory regulation of angiogenesis have, however, not yet been explored.…”

A Temporarily Distinct Subpopulation of Slow-Cycling Melanoma Cells Is Required for Continuous Tumor Growth

“…The inverse expression of JARID1B, JAG1, and HEY1/2 amongst neighboring cells is reminiscent of the concept of lateral inhibition where reciprocal stimulation/inhibition of Notch signaling dynamically leads to the maintenance of neuroectodermal stem cells (Kageyama et al, 2008). During differentiation of neuroprogenitors, N ic levels were reported to oscillate resulting in a steadily increasing and decreasing activation of downstream targets (Kageyama et al, 2009). Thus, we suggest that together with JAG1/Notch 1, JARID1B is part of a complex dynamic program of stemness regulation in melanoma.…”

Sox9 Is Upstream of MicroRNA-140 in Cartilage

“…It is common that a gene regulated by another one can have a feed-back regulation (25). Thus, we next tested if miR-140 affects the expression of Sox9 in zebrafish.…”