Nitric oxide coordinates cell proliferation and cell movements during early development of Xenopus.
The establishment of a vertebrate body plan during embryogenesis is achieved through precise coordination of cell proliferation and morphogenetic cell movements. Here we show that nitric oxide (NO) suppresses cell division and facilitates cell movements during early development of Xenopus, such that inhibition of NO synthase (NOS) increases proliferation in the neuroectoderm and suppresses convergent extension in the axial mesoderm and neuroectoderm. NO controls cell division and cell movement through two separate signaling pathways. Both rely on RhoA-ROCK signaling but can be distinguished by the involvement of either guanylate cyclase or the planar cell polarity regulator Dishevelled. Through the cGMP-dependent pathway, NO suppresses cell division by negatively regulating RhoA and controlling the nuclear distribution of ROCK and p21WAF1. Through the cGMP-independent pathway, NO facilitates cell movement by regulating the intracellular distribution and level of Dishevelled and the activity of RhoA, thereby controlling the activity of ROCK and regulating actin cytoskeleton remodeling and cell polarization. Concurrent control by NO helps ensure that the crucial processes of cell proliferation and morphogenetic movements are coordinated during early development.
Peunova
Natalia
N
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. peunova@cshl.edu
Scheinker
Vladimir
V
Ravi
Kandasamy
K
Enikolopov
Grigori
G
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D006152:Cyclic GMP / Q000378:metabolism; D000072261:Dishevelled Proteins; D008648:Mesoderm / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D015398:Signal Transduction; D014982:Xenopus laevis / Q000196:embryology / Q000502:physiology*; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D006152:Cyclic GMP