Small-molecule inhibitors can be used as loss-of-function tools to investigate the molecular mechanisms of development but, although exposure to these inhibitors can be temporally controlled, their effects are not spatially restricted. Now, Nanette Nascone-Yoder and colleagues have generated a pharmacological agent that allows for photoactivatable, and hence spatiotemporally limited, inhibition of Rho kinase (see p. ). Rho signalling is involved in many morphogenetic events, including primitive gut elongation in Xenopus embryos. The researchers install a photolabile‘caging’ group on Rockout, a small-molecule inhibitor of Rho kinase, and show that caged Rockout (cRO) can permeate Xenopus embryonic tissues. When cultured in the dark, cRO-treated embryos develop normally, but UV irradiation of the right side of these embryos produces animals with a unilaterally shortened gut. Finally, the use of cRO reveals a differential requirement for Rho signalling on the left and right sides of the gut during intestinal rotation. Photocaging pharmacological inhibitors, the researchers conclude, might be a generalisable technique for producing loss-of-function reagents for use in multiple developmental contexts.
