Proximo-distal Axis

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Shown are two temporal series of leg discs. The series stained in blue/green/red show leg discs stained for dpp-lacZ (green), Wg (blue) and the Leg-Trigger-lacZ reporter gene (red). The series stained in yellow/light blue/red show leg discs stained for Hth (yellow), Dll (light blue) and the Leg-Trigger-lacZ reporter (red). See Estella and Mann (2008) and Estella et. al. (2008) for details.

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Proximal-distal axis formation of the appendages

In addition to having anterior-posterior and dorsal-ventral axes, appendages have a proximal-distal (PD) axis that stems from the base of the appendage to its tip. Exd and Hth, in addition to being Hox cofactors, are also important for specifying the proximal identities of the appendages. In addition, these factors work with another transcription factor, Teashirt (Tsh), to specify proximal identities. Other transcription factors, such as Distalless (Dll) and Dachshund (Dac) in the legs and Vestigial in the wing, are important for specifying intermediate and distal fates in the appendages.

The expression of these transcription factors is controlled, at least in part, by two signaling pathways, Wingless (Wg) and Decapentaplegic (Dpp). It is thought that high levels of activity of these two signals is required for specifying distal fates, and gradually lower levels is required for specifying intermediate and proximal fates.

We are interested in understanding how the transcription factors that are expressed in discreet domains along the proximal-distal axis interact with the signaling pathways to specify unique fates. Further, we are studying how the expression domains of these factors are generated and maintained during development of this axis. Recently, we have uncovered a novel mechanism by which the combined activities of Wg and Dpp induce the expression of Dll and dac. According to this model, Wg and Dpp initiate the expression of these two PD genes at unique concentrations. Once activated, both targets are maintained in a Wg and Dpp-independent manner. See the two papers (Estella and Mann 2008, and Estella et. al., 2008) for the complete story.

We also continue to study the PD axis in wing development; see papers by Zirin and Mann (2004, 2007) for our most recent publications.

Relevant papers:

Abu-Shaar, M. and R. S. Mann (1998) Generation of multiple antagonistic domains along the proximo-distal axis during Drosophila leg development. Development, 125, 3821-3830.

Casares, F. and R.S. Mann (2001). The ground state of the ventral appendage in Drosophila. Science, 293:1477-1480.

Mann R.S. and F. Casares (2002) Developmental biology: Signalling legacies. Nature 418:737-739.

Zirin JD and Mann RS (2004) Differing strategies for the establishment and maintenance of teashirt and homothorax repression in the Drosophila wing. Development. Nov;131(22):5683-93.

Zirin, JD and Mann, RS. (2007) Nubbin and Teashirt mark barriers to clonal growth along the proximal-distal axis of the Drosophila wing. Dev Biol. 2007 Apr 15;304(2):745-58.

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) in press.

Estella, C. and Mann, R.S. Logic of Wg and Dpp induction of distal and medial fates in the Drosophila leg. Development, 2008, in press.


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