The neuronal architecture of Xenopus retinal ganglion cells is sculpted by rho-family GTPases in vivo.
Dendritogenesis, axonogenesis, pathfinding, and target recognition are all affected in distinct ways when Xenopus retinal ganglion cells (RGCs) are transfected with constitutively active (ca), wild-type (wt), and dominant negative (dn) Rho-family GTPases in vivo. Dendritogenesis required Rac1 and Cdc42 activity. Moreover, ca-Rac1 caused dendrite hyperproliferation. Axonogenesis, in contrast, was inhibited by ca-Rac1. This phenotype was partially rescued by the coexpression of dn cyclin-dependent kinase (Cdk5), a proposed effector of Rac1, suggesting that Rac1 activity must be regulated tightly for normal axonogenesis. Growth cone morphology was particularly sensitive to dn-RhoA and wt-Cdc42 constructs. These also caused targeting errors, such as tectal bypass, suggesting that cytoskeletal rearrangements are involved in target recognition and are transduced by these pathways.
Ruchhoeft
M L
ML
Biology Department, University of California at San Diego, La Jolla, California 92093-0357, USA.
Ohnuma
S
S
McNeill
L
L
Holt
C E
CE
Harris
W A
WA
D000818:Animals; D001369:Axons / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000502:physiology; D003712:Dendrites / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000502:physiology; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000502:physiology*; D014162:Transfection; D014982:Xenopus laevis; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
D018797:Cell Cycle Proteins; D011993:Recombinant Fusion Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein