Molecular Integration of Wingless, Decapentaplegic, and Autoregulatory Inputs into Distalless during Drosophila Leg Development

Estella, Carlos; McKay, Daniel J.; Mann, Richard S.

doi:10.1016/j.devcel.2007.11.002

Cited by 97 publications

(144 citation statements)

References 51 publications

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“…Once both Dll and dac are activated, even in the same cell, we imagine that they, too, become locked into an expressed state by an autoregulatory and/or Polycomb-dependent mechanism. A recent analysis of the cis-regulatory elements controlling Dll expression in the Drosophila leg is consistent with this model (Estella et al, 2008). In particular, Dll expression in the leg disc uses two cis-regulatory elements.…”

Section: Revised Model For Pd Axis Formationmentioning

confidence: 57%

“…Importantly, Brk plays a crucial role in this model because it keeps Dll switched off in a large part of the disc, thus allowing Wg-mediated activation of Dll to occur in only a small subset of the disc. Consistently, a Dll enhancer that activates expression in the young leg disc directly integrates Wg and Dpp inputs by binding Tcf, Mad and Brk (Estella et al, 2008). In addition to these inputs, there must be additional factors that limit Dll activation to ventral, but not dorsal (e.g.…”

Section: Signal Integration Into Dll and Dacmentioning

confidence: 98%

“…One directly receives input from Wg and Dpp and, consequently, is only active in the center of the leg disc where both signals meet. The second element maintains this initial expression at least in part by via an autoregulatory mechanism, by directly binding Dll (Estella et al, 2008). In the future, it will be important to further test the model proposed here by analyzing the regulatory elements controlling dac during leg development.…”

Section: Revised Model For Pd Axis Formationmentioning

confidence: 99%

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Logic of Wg and Dpp induction of distal and medial fates in theDrosophilaleg

Estella

Mann

2008

Development

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Animal body plans require the specification of unique cell fates along two primary axes: anteroposterior (AP) and dorsoventral (DV). In addition, for those animals bearing appendages, a third, proximodistal (PD), axis must be generated orthogonal to the primary body axes. Studies in Drosophila have revealed many of the signals and pathways that control the formation of these three axes (reviewed by Morata, 2001). However, as many of the same pathways are used for forming all three of these axes, it remains unclear how they are uniquely specified. Moreover, once established, it is not understood how positional information is specified along an the PD axis of an appendage.In Drosophila, the appendages are derived from imaginal discs, sheets of epithelial cells that are patterned during larval development. Imaginal discs are divided into anterior (A) and posterior (P) compartments, groups of cells that are segregated from each other early in development (Lawrence and Morata, 1977). Compartment boundaries are sources of signaling molecules, morphogens, that provide positional information to the cells in the developing discs (Tabata and Takei, 2004). In the leg disc, Hedgehog (Hh) is expressed and secreted by cells of the P compartment, and induces the expression of two long-range signaling molecules, Decapentaplegic (Dpp) and Wingless (Wg), in A compartment cells that are adjacent to the AP compartment boundary. Hh activates dpp in the dorsal half of the leg disc and wg in the ventral half (Basler and Struhl, 1994). Once activated, the wg and dpp expression domains are maintained by a mutually antagonistic repression between them (Brook and Cohen, 1996;Jiang and Struhl, 1996;Johnston and Schubiger, 1996;Morimura et al., 1996;Penton and Hoffmann, 1996;Theisen et al., 1996). dpp is required to pattern the dorsal half of the leg (Morimura et al., 1996;Theisen et al., 1996), whereas wg is required to specify ventral leg fates (Couso et al., 1993;Johnston and Schubiger, 1996;Struhl and Basler, 1993;Wilder and Perrimon, 1995) (Fig. 1A). Thus, the DV axis of the leg is specified by these two opposing morphogens, probably by regulating unique sets of target genes in a concentration-dependent manner (Abu-Shaar and Mann, 1998;Brook and Cohen, 1996;Hays et al., 1999).In contrast to the DV axis, Dpp and Wg act combinatorially to generate the proximodistal (PD) axis of the leg by inducing a different set of target genes, including Distalless (Dll) and dachshund (dac) (Campbell et al., 1993;Diaz-Benjumea et al., 1994;Lecuit and Cohen, 1997;Mardon et al., 1994) (Fig. 1A). Unlike Wg and Dpp, which are expressed in ventral and dorsal sectors of the leg disc, respectively, Dll and dac are expressed in approximately circular domains whose centers are located where the Wg and Dpp sectors meet in the middle of the disc (Fig. 1A). Dll is expressed in a large central domain of the leg disc that gives rise to the distalmost positions of the adult leg (tarsus and distal tibia), whereas dac is expressed in more medial PD positions. It has be...

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Section: Revised Model For Pd Axis Formationmentioning

confidence: 57%

Section: Signal Integration Into Dll and Dacmentioning

confidence: 98%

Section: Revised Model For Pd Axis Formationmentioning

confidence: 99%

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Logic of Wg and Dpp induction of distal and medial fates in theDrosophilaleg

Estella

Mann

2008

Development

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“…As mentioned in previous sections, this gene contains cis-regulatory elements, able to work in isolation, that are active in D. melanogaster leg discs. These regulatory elements are separated by 12 Kb of DNA without enhancer activity in leg discs (Estella et al, 2008). A recent study revealed that at least four different regions within these 12 Kb harbor functional binding sites for the transcription factor GAF ( Fig.…”

Section: The Unknown Spatial Distribution Of Cis-regulatory Informationmentioning

confidence: 99%

“…In this organ, part of the expression pattern of the gene Distalless (Dll) is controlled by two distant enhancers named LT and M. These two enhancers drive very different expression patterns, and none of them alone recapitulates Dll native expression in the leg disc (Estella et al, 2008). However, when these two elements are combined in a lacZ reporter construct, the enhancer duo drives expression in all Dll-expressing cells (Estella et al, 2008). A similar behavior has been observed in the gene sloppy-paired-1 during Drosophila embryonic development (Prazak et al, 2010).…”

Section: Developmental Dynamicsmentioning

confidence: 99%

Multiple layers of complexity in cis‐regulatory regions of developmental genes

Frankel

2012

Developmental Dynamics

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Genomes contain the necessary information to ensure that genes are expressed in the right place, at the right time, and with the proper rate. Metazoan developmental genes often possess long stretches of DNA flanking their coding sequences and/or large introns which contain elements that influence gene expression. Most of these regulatory elements are relatively small and can be studied in isolation. For example, transcriptional enhancers, the elements that generate the expression pattern of a gene, have been traditionally studied with reporter constructs in transgenic animals. These studies have provided and will provide invaluable insights into enhancer evolution and function. However, this experimental approach has its limits; often, enhancer elements do not faithfully recapitulate native expression patterns. This fact suggests that additional information in cis-regulatory regions modulates the activity of enhancers and other regulatory elements. Indeed, recent studies have revealed novel functional aspects at the level of whole cis-regulatory regions. First, the discovery of ''shadow enhancers.'' Second, the ubiquitous interactions between cis-regulatory elements. Third, the notion that some cis-regulatory regions may not function in a modular manner. Last, the effect of chromatin conformation on cis-regulatory activity. In this article, I describe these recent findings and discuss open questions in the field.

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Imaginal discs: Renaissance of a model for regenerative biology

et al. 2010

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Many animals display a capacity to regenerate tissues or even a complete body. One of the main goals of regenerative biology is to identify the genes and genetic networks necessary for this process. Drosophila offers an ideal model system for such studies. The wide range of genetic and genomic approaches available for use in flies has helped in initiating the deciphering of the mechanisms underlying regeneration, and the results may be applicable to other organisms, including mammals. Moreover, most models of regeneration require experimental manipulation, whereas in Drosophila discrete domains can be ablated by genetically induced methods. Here, we present a summary of current research into imaginal disc regeneration and discuss the power of this tissue as a tool for understanding the genetics of regeneration.

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Molecular Integration of Wingless, Decapentaplegic, and Autoregulatory Inputs into Distalless during Drosophila Leg Development

Cited by 97 publications

References 51 publications

Logic of Wg and Dpp induction of distal and medial fates in theDrosophilaleg

Logic of Wg and Dpp induction of distal and medial fates in theDrosophilaleg

Multiple layers of complexity in cis‐regulatory regions of developmental genes

Imaginal discs: Renaissance of a model for regenerative biology

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