Healing

Hh-Gli signalling in epithelial stem cells and regeneration

Hh-Gli signaling is a key player in the control of stem cell behavior and HEALING focuses on two tissues in two model systems: mammals and flies.

The mammalian brain: Injuries of adult mammalian CNS (e.g. ischemia, traumatic injury) cause severe losses of function whose repair has long been thought to be ineffective. However, a limited repair response (cell regeneration, axonal sprouting of surviving neurons and new synapse formation) may occur, and enhanced neurogenesis from post-embryonic resident neural stem/progenitor cells appears to play an important role.

The mammalian skin: Whenever an organism sustains an injury, effective and rapid restoration of the skin barrier function is fundamental for survival. The epidermis is a multilayered epithelium in which terminally differentiated cells are continually shed and replaced throughout adult life. Hair follicles undergo cyclic periods of degeneration (catagen), rest (telogen) and regeneration (anagen). In both cases, the regeneration phase is sustained by stem cell populations residing in the bulge region of the hair follicle and in the interfollicular epidermis (reviewed in Watt et al., 2006). During the hair cycle Shh expression and Hh-Gli signaling are spatially and temporally regulated and restricted to anagen that is blocked by inhibition of Shh. A major activity of Hh signaling is to promote cell proliferation via enhancement of cell cycle re-entry (G1/S transition).