A limitation of our study is the lack of clinical outcome data

affects trophoblast fusion, myoblast fusion or wound healing in vivo, as has been suggested, remains to be determined. In summary, here we have identified calponin-3 as a putative element downstream of preBCR signaling. Deletion of calponin-3 in B cells, however, did not lead to a profound phenotype, arguing against an important role in B cell development. Nevertheless, the mouse model we generated in the course of this project will be of benefit for assessing the role of calponin-3 under physiological conditions. It not only simplifies the identification and tracking of calponin-3-expressing cells in vivo, but also allows its analysis in a loss-of-function approach. Crossing our mice with a Cre-transgenic strain of choice will reveal the tissue-specific function of calponin-3, and thus will help to shed light on the role of calponin-3 in muscle and nonmuscle cells. ~~ Melanogenesis is the physiological process by which melanin is synthesized in melanocytes located in the basal layer of the epidermis to protect the skin from UV irradiation. UVB-exposed keratinocytes secrete cytokines and growth factors, including endothelin 1, that stimulate cellular functions, especially proliferation and melanization, of adjacent melanocytes in the epidermis. The corresponding specific receptors are constitutively expressed by human melanocytes and the binding of cytokines and growth factors to their receptors transduces intracellular 518303-20-3 signals to initiate melanogenesis through specific signaling cascades. On the other hand, UVB radiation directly induces the generation of reactive oxygen species in epidermal keratinocytes and melanocytes and stimulates stress activated protein kinases, such as p38, c-jun N-terminal kinase or extracellular regulated protein kinase . In UVB-exposed human melanocytes, the p38 pathway predominantly contributes to the increased expression of microphthalmia-associated transcription factor , a master regulator of melanocyte functions, including differentiation, proliferation, survival and melanogenesis. MITF regulates the expression of many melanogenic enzymes, melanosome structural proteins, transporters and receptors, such as tyrosinase, tyrosinase-related protein 1, dopachrome tautomerase, melanosomal protein 17, melanoma antigen recognized by T-cells 1 and endothelin B-receptor . EDN-EDNRB binding is one of the key paracrine interactions between keratinocytes and melanocytes that regulates skin pigmentation. EDN1 is a vasoconstrictor PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19696148 peptide originally isolated from porcine endothelial cells. We first reported that human keratinocytes produce a prepro-EDN1 and then convert it by metallo-proteinases including EDN-converting enzyme, sequentially to big-EDN1 and EDN1, which is the final secretable form. UVB-exposed human keratinocytes distinctly enhance the secretion of EDN1, which triggers adjacent melanocytes in the epidermis via EDNRB to stimulate melanin synthesis. EDNRB is a seven-transmembrane receptor coupled with G-protein that interacts PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19697345 equally with all forms of EDN, EDN-1, EDN-2 and EDN-3. Mutations of those genes causes Waardenburg Syndrome Type IV, which is an auditory-pigmentary syndrome characterized by hearing loss, abnormal pigmentation of skin, hair and eyes in association with Hirschsprung disease, which is a disorder that causes blockage of the intestine. The role of the EDN-EDNRB interaction was reported to induce mitogenesis and melanogenesis in melanocytes. Although EDN secretion from keratinocytes sti