Publication:
Free Text: 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.

Related Articles
jing is required for wing development and to establish the proximo-distal axis of the leg in Drosophila melanogaster.
Genetics. 2006
jing is required for wing development and to establish the proximo-distal axis of the leg in Drosophila melanogaster.
Culi J, Aroca P, Modolell J, Mann RS. Genetics. 2006 May; 173(1):255-66. Epub 2006 Mar 1.
Regulation of the twist target gene tinman by modular cis-regulatory elements during early mesoderm development.
Development. 1997
Regulation of the twist target gene tinman by modular cis-regulatory elements during early mesoderm development.
Yin Z, Xu XL, Frasch M. Development. 1997 Dec; 124(24):4971-82.
Review A dynamic network of morphogens and transcription factors patterns the fly leg.
Curr Top Dev Biol. 2012
Review A dynamic network of morphogens and transcription factors patterns the fly leg.
Estella C, Voutev R, Mann RS. Curr Top Dev Biol. 2012; 98:173-98.
A complex role for distal-less in crustacean appendage development.
Dev Biol. 2002
A complex role for distal-less in crustacean appendage development.
Williams TA, Nulsen C, Nagy LM. Dev Biol. 2002 Jan 15; 241(2):302-12.
Review Combinatorial transcriptional regulation: the interaction of transcription factors and cell signaling molecules with homeodomain proteins in Drosophila development.
Crit Rev Eukaryot Gene Expr. 2...
Review Combinatorial transcriptional regulation: the interaction of transcription factors and cell signaling molecules with homeodomain proteins in Drosophila development.
Bondos SE, Tan XX. Crit Rev Eukaryot Gene Expr. 2001; 11(1-3):145-71.
Developmental regulation of chromatin conformation by Hox proteins in Drosophila.
Cell Rep. 2012
Developmental regulation of chromatin conformation by Hox proteins in Drosophila.
Agelopoulos M, McKay DJ, Mann RS. Cell Rep. 2012 Apr 5; 1(4):350-359.
Establishment of medial fates along the proximodistal axis of the Drosophila leg through direct activation of dachshund by Distalless.
Dev Cell. 2011
Establishment of medial fates along the proximodistal axis of the Drosophila leg through direct activation of dachshund by Distalless.
Giorgianni MW, Mann RS. Dev Cell. 2011 Apr 19; 20(4):455-68.
Review Pbx homeodomain proteins: TALEnted regulators of limb patterning and outgrowth.
Dev Dyn. 2011
Review Pbx homeodomain proteins: TALEnted regulators of limb patterning and outgrowth.
Capellini TD, Zappavigna V, Selleri L. Dev Dyn. 2011 May; 240(5):1063-86. Epub 2011 Mar 17.