Parallel labeled-line organization of sympathetic outflow for selective organ regulation in mice.

The sympathetic nervous system is crucial for responding to environmental changes. This regulation is coordinated by the spinal sympathetic preganglionic neurons (SPNs), innervating both postganglionic neurons and the adrenal gland. Despite decades of research supporting the concept of selective control within this system, the neural circuit organization responsible for the output specificity remains poorly understood.

High Hes1 expression and resultant Ascl1 suppression regulate quiescent vs. active neural stem cells in the adult mouse brain.

Somatic stem/progenitor cells are active in embryonic tissues but quiescent in many adult tissues. The detailed mechanisms that regulate active versus quiescent stem cell states are largely unknown. In active neural stem cells, Hes1 expression oscillates and drives cyclic expression of the proneural gene , which activates cell proliferation.

Visualization of Notch signaling oscillation in cells and tissues.

The Notch signaling effectors Hes1 and Hes7 exhibit oscillatory expression with a period of about 2-3 h during embryogenesis. Hes1 oscillation is important for proliferation and differentiation of neural stem cells, whereas Hes7 oscillation regulates periodic formation of somites. Continuous expression of Hes1 and Hes7 inhibits these developmental processes.

The roles and mechanism of ultradian oscillatory expression of the mouse Hes genes.

Somites, metameric structures, give rise to the vertebral column, ribs, skeletal muscles and subcutaneous tissues. In mouse embryos, a pair of somites is formed every 2h by segmentation of the anterior parts of the presomitic mesoderm. 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.

Oscillatory control of factors determining multipotency and fate in mouse neural progenitors.

The basic helix-loop-helix transcription factors Ascl1/Mash1, Hes1, and Olig2 regulate fate choice of neurons, astrocytes, and oligodendrocytes, respectively. These same factors are coexpressed by neural progenitor cells. Here, we found by time-lapse imaging that these factors are expressed in an oscillatory manner by mouse neural progenitor cells.

Oscillatory gene expression and somitogenesis.

A bilateral pair of somites forms periodically by segmentation of the anterior ends of the presomitic mesoderm (PSM). This periodic event is regulated by a biological clock called the segmentation clock, which involves cyclic gene expression. Expression of her1 and her7 in zebrafish and Hes7 in mice oscillates by negative feedback, and mathematical models have been used to generate and test hypotheses to aide elucidation of the role of negative feedback in regulating oscillatory expression.

Oscillatory links of Fgf signaling and Hes7 in the segmentation clock.

Somitogenesis is controlled by the segmentation clock, where the oscillatory expression of cyclic genes such as Hes7 leads to the periodic expression of Mesp2, a master gene for somite formation. Fgf signaling induces the oscillatory expression of Hes7 while Hes7 drives coupled oscillations in Fgf and Notch signaling, which inhibits and activates Mesp2 expression, respectively. Because of different oscillatory dynamics, oscillation in Fgf signaling dissociates from oscillation in Notch signaling in S-1, a prospective somite region, where Notch signaling induces Mesp2 expression when Fgf signaling becomes off.

Accelerating the tempo of the segmentation clock by reducing the number of introns in the Hes7 gene.

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.