Fig. 7. Summary diagram for hair shaft differentiation and hair cycle regulators. (A) Regulators and check points at each hair cycle phase transition. In essence, the hair cycle is orchestrated by molecules that regulate the transition between anagen-catagen, catagen-telogen and telogen-anagen. Each checkpoint is likely to be regulated by a group of factors. Some promote and some suppress the transition. The observed length of each hair cycle phase reflects the summation of the activities that promote or suppress the entry to the next phase. In the Msx2 knockout mutants, catagen starts earlier and lasts longer, and telogen hair has difficulty re-entering anagen. Therefore, it is most likely that the normal role of Msx2 in hair cycling is to maintain hairs in anagen phase. (B) Role of Msx2 in hair shaft differentiation. Upon induction of dermal papilla, stem cells in outer root sheath (ORS) generate TA cells that migrate to the matrix region. TA cells proliferate to generate cellular masses for making differentiated hair structures, and the regulation of this cellular flow can determine the size of hairs (Wang et al., 1999). The specified cell types are arranged in concentric layers from outside to inside. Several major molecular pathways are known to be involved in this specification and differentiation process (see text for detail). Msx2 is one of the central integrators that transmits growth factor signals to regulate hair differentiation.

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