Accelerating the Tempo of the Segmentation Clock by Reducing the Number of Introns in the Hes7 Gene

Abstract

Periodic somite segmentation is controlled by the cyclic gene Hes7, whose oscillatory expression depends upon negative feedback with a delayed timing. The mechanism that regulates the pace of segmentation remains to be determined, but mathematical modeling has predicted that negative feedback with shorter delays would give rise to dampened but more rapid oscillations. Here, we show that reducing the number of introns within the Hes7 gene shortens the delay and results in a more rapid tempo of both Hes7 oscillation and somite segmentation, increasing the number of somites and vertebrae in the cervical and upper thoracic region. These results suggest that the number of introns is important for the appropriate tempo of oscillatory expression and that Hes7 is a key regulator of the pace of the segmentation clock.