| First Author | Üstün Y | Year | 2019 |
| Journal | Matrix Biol | Volume | 80 |
| Pages | 59-71 | PubMed ID | 30273664 |
| Mgi Jnum | J:282279 | Mgi Id | MGI:6378371 |
| Doi | 10.1016/j.matbio.2018.09.006 | Citation | Ustun Y, et al. (2019) Dual role of laminin511 in regulating melanocyte migration and differentiation. Matrix Biol 80:59-71 |
| abstractText | Laminins are the major basement membrane (BM) components and are heterotrimers composed of an alpha, a beta and a gamma chain. In skin, laminins are present in basement membranes surrounding vascular structures, nerves, adipose tissue and in the specialized junctional BM between the epidermis and dermis. The main laminin isoforms in the dermo-epidermal BM are laminin332, laminin511 and laminin211, the latter being restricted to hair follicles (HFs). The laminin gamma1 chain is the most abundant gamma chain; its global ablation in mice leads to early embryonic lethality at E5.5. To elucidate the cellular function of the gamma1 chain in skin, we generated mice with keratinocyte-specific deletion of this chain (Lamc1(EKO)) by using the keratin (K)14-Cre/loxP system. These mice showed delayed coat pigmentation despite normal melanocyte counts in the skin. However, levels of differentiation-specific melanocyte enzymes TRP1, TRP2 and tyrosinase were reduced in Lamc1(EKO) mice, and melanocytes failed to migrate to their differentiation niche in HFs and accumulated in the IFE. These results suggested that the pigmentation defect results from impaired melanocyte migration. The impaired migratory capacity of melanocytes is due to the altered composition of laminins in the BM of Lamc1(EKO) mice: Loss of keratinocyte-derived pro-migratory laminin511 is not compensated by ectopically deposited fibroblast-derived laminin211. Furthermore, contact of melanocytes with recombinant laminin511, but not with laminin211, induces the expression of the chemokine receptor CXCR4 on melanocytes, needed for SDF1 (stromal cellderived factor1)-mediated migration into HFs. We here demonstrate that laminin511 controls the differentiation of melanocytes by regulating their migration from the epidermis into HFs and by activating CXCR4 expression on melanocytes required for their recruitment into HFs in an SDF1-dependent manner. |
