Editors' ChoiceDevelopment

Signaling Activity in Vivo

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Science Signaling  09 Jun 2009:
Vol. 2, Issue 74, pp. ec196
DOI: 10.1126/scisignal.274ec196

Spatial and temporal regulation of the activity of ubiquitously expressed proteins is critical to the proper function of signaling pathways. Kamiyama et al. have measured activity of the small, ubiquitously expressed guanosine triphosphatase (GTPase) Cdc42 in intact Drosophila melanogaster embryos during development using fluorescence resonance energy transfer (FRET) analysis with a transgenically encoded probe for Cdc42 activity. Although some Cdc42 activity was observed in scattered cells earlier in embryogenesis, Cdc42 did not display any tissue-wide activation until about 15 hours into development (the time at which organogenesis begins), when it became active in the trachea, the central nervous system (CNS), and a group of cells along the dorsal midline. Both the spatial and temporal patterns of Cdc42 activity corresponded to the tissues and stages affected in cdc42 loss-of-function mutants. The authors also expressed the Cdc42 activity probe specifically in the segmentally reiterated anterior corner cell (aCC) motoneuron to examine Cdc42 activity at the cellular level. Cdc42 became active in this cell after axonal outgrowth was under way in the area of the axon from which dendrites would grow, and activity persisted in this area throughout dendrite elaboration. Removing Cdc42 activity from aCCs had no effect on cellular morphology before the time when Cdc42 activity was observed in wild-type aCCs. Expressing constitutively active Cdc42 in this motoneuron caused premature termination of axonal growth and defects in dendrogenesis, whereas overexpressing wild-type Cdc42 had no effect on morphology. The spatial and temporal pattern of Cdc42 activity thus corresponded with the phenotypes observed in loss-of-function mutants at both an organismal and cellular level. It is striking that this ubiquitously expressed protein is activated in a relatively small portion of the embryo and required for discrete, relatively short periods of time, at least in aCC cells.

D. Kamiyama, A. Chiba, Endogenous activation patterns of Cdc42 GTPase within Drosophila embryos. Science 324, 1338–1340 (2009). [Abstract] [Full Text]

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