Coordinated Control of Cell Adhesion, Polarity, and Cytoskeleton Underlies Hox-Induced Organogenesis in Drosophila

Lovegrove, Bridget; Simões, Sérgio; Rivas, María Luisa; Sotillos, Sol; Johnson, Kevin M.; Knust, Elisabeth; Jacinto, António; Hombría, James Castelli-Gair

doi:10.1016/j.cub.2006.09.029

Cited by 90 publications

(152 citation statements)

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“…However, there is also evidence for other modes of Hox gene action (4)(5)(6)(7)(8). For example, the role of Abdominal B in Drosophila posterior spiracles is more akin to that of a master control gene (30). In this context, the Hox protein activates a set of primary regulators at a specific time in development to initiate a novel organ.…”

Section: Discussionmentioning

confidence: 99%

Hox gene Ultrabithorax regulates distinct sets of target genes at successive stages of Drosophila haltere morphogenesis

Pavlopoulos

Akam

2011

Proc. Natl. Acad. Sci. U.S.A.

109

125

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Hox genes encode highly conserved transcription factors that regionalize the animal body axis by controlling complex developmental processes. Although they are known to operate in multiple cell types and at different stages, we are still missing the batteries of genes targeted by any one Hox gene over the course of a single developmental process to achieve a particular cell and organ morphology. The transformation of wings into halteres by the Hox gene Ultrabithorax (Ubx) in Drosophila melanogaster presents an excellent model system to study the Hox control of transcriptional networks during successive stages of appendage morphogenesis and cell differentiation. We have used an inducible misexpression system to switch on Ubx in the wing epithelium at successive stages during metamorphosis-in the larva, prepupa, and pupa. We have then used extensive microarray expression profiling and quantitative RT-PCR to identify the primary transcriptional responses to Ubx. We find that Ubx targets range from regulatory genes like transcription factors and signaling components to terminal differentiation genes affecting a broad repertoire of cell behaviors and metabolic reactions. Ubx up-and downregulates hundreds of downstream genes at each stage, mostly in a subtle manner. Strikingly, our analysis reveals that Ubx target genes are largely distinct at different stages of appendage morphogenesis, suggesting extensive interactions between Hox genes and hormone-controlled regulatory networks to orchestrate complex genetic programs during metamorphosis.appendage specialization | homeotic genes | serial homology

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Section: Discussionmentioning

confidence: 99%

Hox gene Ultrabithorax regulates distinct sets of target genes at successive stages of Drosophila haltere morphogenesis

Pavlopoulos

Akam

2011

Proc. Natl. Acad. Sci. U.S.A.

109

125

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“…Loss of Hox genes has been found in certain cases to result in the loss of particular tissues (Lovegrove et al, 2006;Mandeville et al, 2006;Hostikka et al, 2009;Le Pabic et al, 2010). There is some evidence indicating the role of Hox genes during kidney development (reviewed by Patterson and Potter, 2003;Costantini and Kopan, 2010;Wellik, 2011).…”

Section: Discussionmentioning

confidence: 99%

Comparative spatiotemporal analysis of Hox gene expression in early stages of intermediate mesoderm formation

Barak

Noon

Reshef

2012

Developmental Dynamics

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Background: Hox genes are key players in AP patterning of the vertebrate body plan and are necessary for organogenesis. Several studies provide evidence for the role Hox genes play during kidney development and especially regarding metanephros initiation and formation. However, the role Hox genes play during early stages of kidney development is largely unknown. A recent study in our lab revealed the role Hoxb4 plays in conferring the competence of intermediate mesodermal cells to respond to kidney inductive signals and express early kidney regulators. Results: As a first step in understanding the role Hox genes play in setting the formation of the pronephros morphogenetic field and the expression of early regulators of kidney development, we studied in detail the expression pattern of 10 Hox genes in relation to the 6th somite axial level, the anterior sharp border of the kidney field. Despite the idea of spatial co-linearity as exemplified in the Hox gene expression pattern in late developmental stages, a very dynamic spatio-temporal expression of these genes was found in early stages. Conclusions: Since mesodermal patterning occurs at gastrula stages, the relevance of a ''Hox code'' at early stages is questioned in this study.

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“…Ideas for how a transcription factor might control programs of cell differentiation have been developed, for example, in the analysis of Hox gene function (20)(21)(22)(23). It could directly activate many target genes required for the differentiation program, or it could function in a hierarchical system in which it directly regulates only a small number of genes, which then regulate the bulk of the required genes.…”

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confidence: 99%

mef2 activity levels differentially affect gene expression during Drosophila muscle development

Elgar

Han

Taylor

2008

Proc. Natl. Acad. Sci. U.S.A.

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Cell differentiation is controlled by key transcription factors, and a major question is how they orchestrate cell-type-specific genetic programs. Muscle differentiation is a well studied paradigm in which the conserved Mef2 transcription factor plays a pivotal role. Recent genomic studies have identified a large number of mef2-regulated target genes with distinct temporal expression profiles during Drosophila myogenesis. However, the question remains as to how a single transcription factor can control such diverse patterns of gene expression. In this study we used a strategy combining genomics and developmental genetics to address this issue in vivo during Drosophila muscle development. We found that groups of mef2-regulated genes respond differently to changes in mef2 activity levels: some require higher levels for their expression than others. Furthermore, this differential requirement correlates with when the gene is first expressed during the muscle differentiation program. Genes that require higher levels are activated later. These results implicate mef2 in the temporal regulation of muscle gene expression, and, consistent with this, we show that changes in mef2 activity levels can alter the start of gene expression in a predictable manner. Together these results indicate that Mef2 is not an all-or-none regulator; rather, its action is more subtle, and levels of its activity are important in the differential expression of muscle genes. This suggests a route by which mef2 can orchestrate the muscle differentiation program and contribute to the stringent regulation of gene expression during myogenesis. muscle differentiation program ͉ transcription factor levels F or several decades it has been appreciated that the controlled regulation of gene expression, including the coordinated activation of batteries of genes, lies behind cell differentiation programs (1-3). It is now clear that a principle tier of control of cell differentiation is through key transcription factors, and an important general question is how these factors coordinate the genetic program of such complex processes. A classic paradigm is muscle, in which the conserved Mef2 transcription factor is a major regulator of gene expression and differentiation (4). Mef2 was first identified in mammalian cell culture (5-7), but because mammals possess four closely related mef2 genes functional analyses during development are complicated. In contrast, Drosophila has a single mef2 gene and was the first organism to be used to show that mef2 is required for muscle development in vivo (8)(9)(10). This highlighted that the analysis of how mef2 functions is central to understanding how muscle is made. Important characteristics of the underlying genetic program include the temporal coordination of muscle gene expression (11-13) and the regulation of levels and relative stoichiometries of gene expression during myogenesis (14-19). Although these basic features have been known for many years, much remains to be understood about them. However, the identificati...

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Coordinated Control of Cell Adhesion, Polarity, and Cytoskeleton Underlies Hox-Induced Organogenesis in Drosophila

Cited by 90 publications

References 50 publications

Hox gene Ultrabithorax regulates distinct sets of target genes at successive stages of Drosophila haltere morphogenesis

Hox gene Ultrabithorax regulates distinct sets of target genes at successive stages of Drosophila haltere morphogenesis

Comparative spatiotemporal analysis of Hox gene expression in early stages of intermediate mesoderm formation

mef2 activity levels differentially affect gene expression during Drosophila muscle development

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