Editors' ChoiceDevelopment

How to Specify a Leg

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Science Signaling  05 Feb 2008:
Vol. 1, Issue 5, pp. ec44
DOI: 10.1126/stke.15ec44

During development, relatively simple signaling mechanisms have been elucidated that explain complicated patterns of distinct cell fates. The anteroposterior (AP) and dorsoventral (DV) axes in particular are derived from gradients in the concentration of morphogens that supply cells with positional information. Animals with limbs have another axis, the proximodistal (PD) axis, that must also be specified, and this results from activity of largely the same group of morphogens and transcriptional regulatory components that control the DV and AP axes, making things more complicated to explain. Estella and Mann use a series of experiments in which they manipulate spatiotemporal aspects of morphogen expression and are able to provide a model that explains how dorsal and ventral gradients of the signaling molecules Decapentaplegic (DPP) and Wingless (Wg) can be converted to circular and concentric domains of expression of two target genes, Distalless (Dll) and dachshund (dac), that control PD cell fate. Unlike in the wing, where the transcriptional repressor Brinker (Brk) is important for DV axis formation, Brk appears not to influence the DV axis in the leg but rather to control the PD axis. Further, the logical interpretation of Dpp signals is shown to be different in the DV and PD axes; that is, Dpp regulates cell fate through distinct transcriptional targets in each axis. In early stages, expression of Dll is dependent on the ratio of Brk activity to the strength of Wg signaling. Later on, the domains of dac and Dll expression become independent of Wg and Dpp. The authors interpret the results to explain formation of the PD axis and the generation of asymmetry in the DV axis of the leg.

C. Estella, R. S. Mann, Logic of Wg and Dpp induction of distal and medial fates in the Drosophila leg. Development 135, 627-636 (2008). [Abstract] [Full Text]