title: The origins of the Drosophila leg revealed by the cis-regulatory architecture of the Distalless gene.
abstract: Limb development requires the elaboration of a proximodistal (PD) axis, which forms orthogonally to previously defined dorsoventral (DV) and anteroposterior (AP) axes. In arthropods, the PD axis of the adult leg is subdivided into two broad domains, a proximal coxopodite and a distal telopodite. We show that the progressive subdivision of the PD axis into these two domains occurs during embryogenesis and is reflected in the cis-regulatory architecture of the Distalless (Dll) gene. Early Dll expression, governed by the Dll304 enhancer, is in cells that can give rise to both domains of the leg as well as to the entire dorsal (wing) appendage. A few hours after Dll304 is activated, the activity of this enhancer fades, and two later-acting enhancers assume control over Dll expression. The LT enhancer is expressed in cells that will give rise to the entire telopodite, and only the telopodite. By contrast, cells that activate the DKO enhancer will give rise to a leg-associated larval sensory structure known as the Keilin's organ (KO). Cells that activate neither LT nor DKO, but had activated Dll304, will give rise to the coxopodite. In addition, we describe the trans-acting signals controlling the LT and DKO enhancers, and show, surprisingly, that the coxopodite progenitors begin to proliferate approximately 24 hours earlier than the telopodite progenitors. Together, these findings provide a complete and high-resolution fate map of the Drosophila appendage primordia, linking the primary domains to specific cis-regulatory elements in Dll.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Integrated Program in Cellular, Molecular, Structural and Genetic Studies, Columbia University, 701 W. 168th Street, HHSC 1104, New York, NY 10032, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: McKay
authors.forename: Carlos
authors.initials: C
authors.lastname: Estella
authors.forename: Richard S
authors.initials: RS
authors.lastname: Mann
mesh_terms: D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000235:genetics*; D035002:Lower Extremity / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C117261:distal-less protein, insect