University of Southern California

Segil Lab

USC Stem Cell

How does the developing inner ear know when to stop growing, and why don’t sensory hair cells regenerate?

How does the developing inner ear know when to stop growing …

Embryonic cochlea from the mouse at ages E12.5, E14.5 and E17.5 have been dissected and stained with an antibody to p27Kip1 (green), which shows an apical to basal gradient of expression. In the upper panel, a marker of cell proliferation is stained red, and a region devoid of staining is outlined by white dots. The lack of cell division corresponds to the region of p27Kip1 staining. (Image courtesy of the Segil Lab)

Embryonic cochlea from the mouse at ages E12.5, E14.5 and E17.5 have been dissected and stained with an antibody to p27Kip1 (green), which shows an apical to basal gradient of expression. In the upper panel, a marker of cell proliferation is stained red, and a region devoid of staining is outlined by white dots. The lack of cell division corresponds to the region of p27Kip1 staining. (Image courtesy of the Segil Lab)

Coordinating cell proliferation, growth and differentiation is crucial for the development of animal form. This project investigates the biochemical machinery responsible for this coordination. We are investigating the role and regulation of cyclin-dependent kinase inhibitors (CKIs) in the formation of the pro-sensory domains in the inner ear, the cells that give rise to the organ of Corti and the vestibular sensory areas. In particular, we are interested in the mechanisms of p27Kip1 gene regulation and its role in timing cell cycle exit.

… and why don’t sensory hair cells regenerate?

Fig. 8 - Web

Restoration of hearing through regeneration will likely require the ability to productively overcome the lifelong cell cycle block that characterizes the cells of the sensory epithelium. Understanding the mechanisms regulating the postmitotic state, and how they might be overcome, is one of the major goals of our work. In this project, we are particularly interested in the mechanisms of cell division control of the progenitors of the hair cells and supporting cells that make up the sensory epithelium. In particular, we are studying the regulation of cell cycle inhibitors, such as p27Kip1, that are responsible not only for initiating cell cycle exit in the developing organ of Corti, but also for maintaining the permanent postmitotic state of the mature supporting cells, the potential targets of regenerative therapy.