Sonic hedgehog and hand

from wikipedia

Role

Members of the hedgehog family play key roles in a wide variety of developmental processes.^[13] One of the best studied examples is the action of Sonic hedgehog during development of the vertebrate limb. The classic experiments of Saunders and Gasseling in 1968 on the development of the chick limb bud formed the basis of the morphogen concept. They showed that identity of the digits in the chick limb was determined by a diffusible factor produced by the zone of polarizing activity (ZPA), a small region of tissue at the posterior margin of the limb. Mammalian development appeared to follow the same pattern. This diffusible factor was later shown to be Sonic hedgehog. However, precisely how SHH determines digit identity remained elusive until recently. The current model, proposed by Harfe et al.,^[25] states that both the concentration and the time of exposure to SHH determines which digit the tissue will develop into in the mouse embryo (figure 6).

Figure 6. Sonic hedgehog specifies digit identity in mammalian development.

Digits V, IV and part of III arise directly from cells that express SHH during embryogenesis. In these cells SHH signals in an autocrine fashion and these digits develop correctly in the absence of DISP, which is required for extracellular diffusion of the ligand. These digits differ in the length of time that SHH continues to be expressed. The most posterior digit V develops from cells that express the ligand for the longest period of time. Digit IV cells express SHH for a shorter time, and digit III cells shorter still. Digit II develops from cells that are exposed to moderate concentrations of extracellular SHH. Finally, digit I development does not require SHH. It is, in a sense, the default program of limb bud cells.

Hedgehog signaling remains important in the adult. Sonic hedgehog has been shown to promote the proliferation of adult stem cells from various tissues, including primitive hematopoieticcells,^[26] mammary^[27] and neural^[28] stem cells. Activation of the hedgehog pathway is required for transition of the hair follicle from the resting to the growth phase.^[29] Curis Inc. together withProcter & Gamble are developing a hedgehog agonist to be used as a drug for treatment of hair growth disorders.^[30] This failed due to toxicities found in animal models.^[31]