Story Of P1P :: '탈모' 태그의 글 목록

Molecular principles of hair follicle induction and morphogenesis

모낭 형성에 중용한 역할을 하는 단백질은 B-Catenin Wnt 단백질임. Wnt 단백질은 모발의 발생과 성장에 관여하는 신호전달 단백질임. Wnt 신호전달이 없으면 epidermal cell fate로 가지만, Wnt 신호전달이 활성화되면 hair follicle fate로 감. Wnt에 의한 신호전달이 B-Catenin으로 이어져 모낭형성이 이루어짐. 따라서 B-Catenin Wnt 단백질의 형성이 탈모치료에 중요한 역할을 담당함.

Our present working hypothesis, for induction of primary (guard; A) and secondary (non-guard, awl; B and C) pelage hair follicles. A: On the left side, the different stages of early hair follicle development are depicted (stage 0–5), according to the original hypothesis of M. Hardy.(6) In mammals, it is not yet known how inductive fields are created prior to initiation of hair follicle placode formation. Thus, the question mark above stage 0. To the right the currently known activation pathways involved in primary guard hair development are shown. Essential inducers are Wnt and EdaA1/EdaR/NF-kB. B: Secondary hair induction calls for Wnt and Noggin. A model concerning inhibition of BMP4 in the dermal papilla and BMP2 in the ectoderm by BMP anatgonist Noggin was proposed by Botchkarev et al.(24) Localized Noggin expression in the dermal papilla antagonizes the potent placode-growth-inhibitory action of the two BMPs and leads to Lef-1 expression. Noggin also inhibits p75NTR expression, which functions as a receptor that negatively regulates hair follicle growth.(94) Jamora et al. go a step further in proposing that Noggin is directly responsible for activation of uclear Lef-1 expression in secondary hair follicles.(33) They suggest that Noggin must counteract any BMP action in the developing follicle because BMP is the key inhibitor of Lef-1 expression. Figure adapted from Botchkarev et al.(24) C: Scheme of the currently known signaling pathways involved in secondary awl hair induction. As shown in B, apart from Wnt signaling, Noggin is the second essential inducer. The numbers (1.–3.) indicate the possible order of events occuring to initiate awl hair development. One major difference of primary guard hairs compared to secondary awl hairs is the EdaA1/EdaR/NF-kB pathway, only activated during initiation of guard hairs. Inhibition of any component of this pathway leads to absence of guard hairs.(22,23) Wnt in both pathways stands for any Wnt, the exact one being unknown. The best-defined so-alled ‘‘inhibitors’’ of hair follicle development, Dkk1 and BMPs, are boxed and marked in black. Dkk1 is a true inhibitor and, ectopically expressed in the ectoderm,it prevents formation of all hair follicle types by complete inhibition of Wnt signaling.(30) However, BMPs do not have a clear inhibitory role. They are in part activators and inhibitors, depending on the developmental stage. BMPs are expressed from early on in both hair types, and at least in secondaryHFstheyseemto be needed for active b-catenin complexes and downstream target gene expression of Wnt/b-catenin/Lef-1.(110,111) The exact role of BMPs in early guard hair follicles remains unknown. However, BMP action may have to be anatgonized by Noggin at later stages of guard hair follicle morphogenesis.(25,112) Shh/Gli2 signaling is activated at a later time point at stage 2–3(hair germ—peg), and is only to a minor degree responsible for dermal papilla formation of both hair types, but seems to be required for dermal Wnt5a expression.(29) Shh/Gli2 is mostly essential for further epidermal downgrowth of the germ and the subsequent peg formation.(12) The formation of secondary zigzag hairs remains to be studied in detail. They seem to demand EdaA1/EdaR/NF-kB signaling later than in guard hairs and further downstream of Wnt/b-catenin and Noggin/Lef-1. Importantly, note that the arrows do not necessarily mean that the protein is directly regulated by a particular pathway, with the exception of Wnt/b-catenin, Eda/NF-kB and Shh/Gli2. In most cases, it means that the indicated protein is activated temporarily downstream. The multiple question marks already imply that there are still many processes that are currently unknown and need to be investigated in the future.

2005, BioEssays




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