Rac1 Drives Melanoblast Organization during Mouse Development by Orchestrating Pseudopod- Driven Motility and Cell-Cycle Progression

• Published in: Developmental cell 2011-10, Vol.21 (4), p.722-734
• Main Authors: Li, Ang, Ma, Yafeng, Yu, Xinzi, Mort, Richard L., Lindsay, Colin R., Stevenson, David, Strathdee, Douglas, Insall, Robert H., Chernoff, Jonathan, Snapper, Scott B., Jackson, Ian J., Larue, Lionel, Sansom, Owen J., Machesky, Laura M.
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Biological and medical sciences; Cell Cycle - physiology; Cell cycle, cell proliferation; Cell differentiation, maturation, development, hematopoiesis; Cell Movement - physiology; Cell physiology; Cell Proliferation; Cells, Cultured; Embryo, Mammalian - cytology; Embryo, Mammalian - metabolism; Epidermal Cells; Epidermis - embryology; Epidermis - metabolism; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Hair Follicle - cytology; Hair Follicle - metabolism; Integrases; Male; Melanocytes - cytology; Melanocytes - metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microtubules - metabolism; Molecular and cellular biology; Myosins - metabolism; Neuropeptides - physiology; Pseudopodia - physiology; rac GTP-Binding Proteins - physiology; rac1 GTP-Binding Protein; Skin - embryology; Skin - metabolism
• ISSN: 1534-5807; 1878-1551; 1878-1551
• DOI: 10.1016/j.devcel.2011.07.008

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. [Display omitted] ► Rac1 and the Scar/WAVE complex drive pseudopod-based motility of melanoblasts ► Rac1-depleted melanoblasts move using unique actin-based stubs and not blebs ► Rac1 controls pseudopod frequency but is dispensable for pseudopod formation ► Loss of Rac1 delays melanoblast cell-cycle progression and cytokinesis