Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Rac1 drives melanoblast organization during mouse development by orchestrating pseudopod- driven motility and cell-cycle progression
AU - Li, Ang
AU - Ma, Yafeng
AU - Yu, Xinzi
AU - Mort, Richard L.
AU - Lindsay, Colin R.
AU - Stevenson, David
AU - Strathdee, Douglas
AU - Insall, Robert H.
AU - Chernoff, Jonathan
AU - Snapper, Scott B.
AU - Jackson, Ian J.
AU - Larue, Lionel
AU - Sansom, Owen J.
AU - Machesky, Laura M.
N1 - Copyright © 2011 Elsevier Inc. All rights reserved.
PY - 2011/10/18
Y1 - 2011/10/18
N2 - 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.
AB - 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.
KW - Actins
KW - Animals
KW - Cell Cycle
KW - Cell Movement
KW - Cell Proliferation
KW - Cells, Cultured
KW - Embryo, Mammalian
KW - Epidermis
KW - Female
KW - Flow Cytometry
KW - Gene Expression Regulation, Developmental
KW - Hair Follicle
KW - Integrases
KW - Male
KW - Melanocytes
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - Microtubules
KW - Myosins
KW - Neuropeptides
KW - Pseudopodia
KW - Skin
KW - rac GTP-Binding Proteins
KW - rac1 GTP-Binding Protein
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.devcel.2011.07.008
DO - 10.1016/j.devcel.2011.07.008
M3 - Journal article
C2 - 21924960
VL - 21
SP - 722
EP - 734
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 4
ER -