Unlike the anterior-posterior (AP) and dorsal-ventral (DV) axes, the proximal-distal (PD) axis must be generated de novo, each time an appendage develops. For the leg, this axis extends from the distal-most tip (the tarsal claw) to the body (proximal). The axis is first formed during embryogenesis and is elaborated during larval development. Key molecular markers for this axis are the homeodomain-encoding gene Distalless (Dll), expressed in the distal-most portion of the leg, the gene dachshund (dac), expressed in medial positions, and homothorax (hth), expressed in the most proximal regions of the appendage and body wall. Our goal is to define the molecular pathways that specify this axis, and our general approach is to identify and characterize the cis-regulatory elements that control the expression of these, and other, PD genes during development. This “bottom-up” approach has revealed a transcription factor cascade that is initially triggered by the joint activities of two secreted morphogens, Wingless (Wg) and Decapentaplegic (Dpp), but is then elaborated by feed-forward loops and autoregulation.
Current lab members working on this project: Roumen Voutev, Susie Tozier.
Susan Newcomb, Roumen Voutev, Aurelie Jory, Rebecca K. Delker, Matthew Slattery, Richard S. Mann cis-regulatory architecture of a short-range EGFR organizing center in the Drosophila melanogaster leg. PLoS Genet 14(8): e1007568. https://doi.org/10.1371/journal.pgen.1007568. August 2018
David Requena, Jose Andres Álvarez, Hugo Gabilondo, Ryan Loker, Richard S. Mann, Carlos Estella Origins and Specification of the Drosophila Wing. http://dx.doi.org/10.1016/j.cub.2017.11.023. December 2017
Oh H, Slattery M, Ma L, Crofts A, White KP, Mann RS, Irvine KD. Genome-wide association of Yorkie with chromatin and chromatin-remodeling complexes. Cell Rep. 2013 Feb 21;3(2):309-18. doi: 10.1016/j.celrep.2013.01.008. Epub 2013 Feb 8. PubMed PMID: 23395637; PubMed Central PMCID: PMC3633442.
Estella C, Voutev R, Mann RS. A dynamic network of morphogens and transcription factors patterns the fly leg. Curr Top Dev Biol. 2012;98:173-98. doi: 10.1016/B978-0-12-386499-4.00007-0. Review. PubMed PMID: 22305163; PubMed Central PMCID: PMC3918458.