title: Rac1 drives melanoblast organization during mouse development by orchestrating pseudopod- driven motility and cell-cycle progression.
abstract: During embryogenesis, melanoblasts proliferate and migrate ventrally through the developing dermis and epidermis as single cells. Targeted deletion of Rac1 in melanoblasts during embryogenesis causes defects in migration, cell-cycle progression, and cytokinesis. Rac1 null cells migrate markedly less efficiently, but surprisingly, global steering, crossing the dermal/epidermal junction, and homing to hair follicles occur normally. Melanoblasts navigate in the epidermis using two classes of protrusion: short stubs and long pseudopods. Short stubs are distinct from blebs and are driven by actin assembly but are independent of Rac1, Arp2/3 complex, myosin, or microtubules. Rac1 positively regulates the frequency of initiation of long pseudopods, which promote migration speed and directional plasticity. Scar/WAVE and Arp2/3 complex drive actin assembly for long pseudopod extension, which also depends on microtubule dynamics. Myosin contractility balances the extension of long pseudopods by effecting retraction and allowing force generation for movement through the complex 3D epidermal environment.
authors.affiliation: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Ma
authors.forename: Xinzi
authors.initials: X
authors.lastname: Yu
authors.forename: Richard L
authors.initials: RL
authors.lastname: Mort
authors.forename: Colin R
authors.initials: CR
authors.lastname: Lindsay
authors.forename: David
authors.initials: D
authors.lastname: Stevenson
authors.forename: Douglas
authors.initials: D
authors.lastname: Strathdee
authors.forename: Robert H
authors.initials: RH
authors.lastname: Insall
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chernoff
authors.forename: Scott B
authors.initials: SB
authors.lastname: Snapper
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Jackson
authors.forename: Lionel
authors.initials: L
authors.lastname: Larue
authors.forename: Owen J
authors.initials: OJ
authors.lastname: Sansom
authors.forename: Laura M
authors.initials: LM
authors.lastname: Machesky
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism; D019426:Integrases; D008297:Male; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008870:Microtubules / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D009479:Neuropeptides / Q000502:physiology*; D011554:Pseudopodia / Q000502:physiology*; D012867:Skin / Q000196:embryology / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000502:physiology*; D020830:rac1 GTP-Binding Protein
chemical_list: D000199:Actins; D009479:Neuropeptides; C484602:Rac1 protein, mouse; C045073:Cre recombinase; D019426:Integrases; D009218:Myosins; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein