RT Journal Article SR Electronic T1 Migration and establishment of progenitor pool of melanocytes is governed by SEMA3E-PLXND1 signaling JF bioRxiv FD Cold Spring Harbor Laboratory SP 2023.02.28.530560 DO 10.1101/2023.02.28.530560 A1 Yogaspoorthi Subramaniam A1 Babita Sharma A1 Ayush Aggarwal A1 Desingu Ayyappa Raja A1 Iti Gupta A1 Madeeha Ghazi A1 Sridhar Sivasubbu A1 Vivek T Natarajan YR 2023 UL http://biorxiv.org/content/early/2023/03/02/2023.02.28.530560.abstract AB Vertebrate pigmentation is an outcome of an interplay of several signaling pathways that result in immense diversity of pigment patterns observed across the animal kingdom. Transitory nature of these signaling events impedes deciphering pathways that control migration and establishment of melanocyte stem cells (McSC), necessary for pigment patterning. Using zebrafish and cultured mammalian melanocytes, we uncover a hitherto unknown role for Plexin D1 signaling. This pathway directs migration by F-actin modulation and further dictates subsequent functional states of melanocytes through a transcriptional response. In zebrafish, abrogation of PLXND1 derails melanocyte migration and reduces mid-line melanophores emerging from the regeneration competent McSC pool. In cultured melanocytes, activation of PLXND1 by the ligand semaphorin 3E reduces the velocity of migration, influences directional correlation, and promotes movement towards positive cues such as SCF. PLXND1 activation results in EGFR signaling necessary for McSC establishment, and induces GNAS, an effector of MC1R pathway involved in melanocyte maturation. Identification of this long-range secreted negative chemotactic signaling provides a missing player and enriches reaction diffusion model for pigment patterning.Competing Interest StatementThe authors have declared no competing interest.