Proximal Distal Axis Formation In The Appendages

Overview of PD axis formation in the fly leg

 

          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

Recent papers:

A dynamic network of morphogens and transcription factors patterns the fly leg. Estella C, Voutev R, Mann RS. Current topics in developmental biology. 2012; 98:173-98. PMID:22305163 PMCID: PMC3918458

A survey of 6,300 genomic fragments for cis-regulatory activity in the imaginal discs of Drosophila melanogaster. Jory A, Estella C, Giorgianni MW, Slattery M, Laverty TR, et al. Cell reports. 2012; 2(4):1014-24. PMID: 23063361 PMCID: PMC3483442

Divergent transcriptional regulatory logic at the intersection of tissue growth and developmental patterning. Slattery M, Voutev R, Ma L, Nègre N, White KP, et al. PLoS genetics. 2013; 9(9):e1003753. PMID: 24039600 PMCID: PMC3764184

 

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 Artist: Carlos Estella

 

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A mid-stage embryo stained for Dll (red) and Hth (blue). The three round expression domains mark the appendage primordia in the three thoracic segments.

 

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A stage 14 embyro stained for Wg (blue), pMad (green, a readout of Dpp signaling), and the Dll (LT)-lacZ reporter gene (red). Expression of LT-lacZ marks the future Dll+dac domains and is triggered by Wg+Dpp signaling. Expression in the abdominal segments is repressed by the abdominal Hox genes.

 

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Six snapshots of leg development, from left to right: embryogenesis, 1st instar larva, 2nd instar larva, 3rd instar larva, pupariation, adult. Images are stained for Hth (blue), Dac (green), and Dll (red).

 

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Evolving relationship between Dpp and Wg during leg development. From left to right: embryogenesis, 1st instar, 2nd instar, early 3rd instar, late 3rd instar. Images are stained for Wg (red) and a reporter for Dpp (green).

 

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Shown is a 3rd instar leg disc stained for Dll (blue), Dac (red and far right panel), and expression from a dac reporter construct, dacHI-lacZ (green and center panel). See Giorgianni and Mann, 2011 for more details.

 

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Representative publications:

 

Estella, C., Voutev, R. and Richard S. Mann, A Dynamic Network of Morphogens and Transcription Factors Patterns the Fly Leg. In Serge Plaza and François Payre, editors: Current Topics in Developmental Biology, Vol. 98, Burlington: Academic Press, 2012, pp. 173-198. PDF

 

Estella, C. and Mann, R.S. Non-redundant selector and growth-promoting functions of two sister genes, buttonhead and Sp1, in Drosophila leg development. PLoS Genet. 2010 Jun 24;6(6):e1001001.  PDF

 

 

Giorgianni, M. and Mann, RS. Establishment of medial fates along the proximodistal axis of the Drosophila leg through direct activation of dachshund by Distalless. Developmental Cell 2011: 19;20(4):455-68.. PDF

 

 

McKay, D., Estella, C. and Mann R.S. The origins of the Drosophila leg as revealed by the cis-regulatory architecture of the Distalless gene. Development. 2009 Jan;136(1):61-71. PDF

 

 

Estella, C., McKay, D., and Mann, R.S. Direct integrations of Wingless, Decapentaplegic, and autoregulatory inputs into Distalless during Drosophila leg development. Dev. Cell, (2008) 14:86-96.

 

 

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

 

 

 

 

 

 

The Laboratory of Richard S Mann
Department of Biochemistry and Molecular Biophysics
Columbia University Medical Center
701 West 168th Street, HHSC 1104
New York, NY 10032
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