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Establishment of a Developmental Compartment Requires Interactions between Three Synergistic -regulatory Modules


The separation of cell populations into distinct functional units is essential for both vertebrate and invertebrate animal development. A classical paradigm for this phenomenon is the establishment of developmental compartments during Drosophila wing development. These compartments depend on the restricted expression of two selector genes, engrailed in the posterior compartment and apterous (ap) in the dorsal compartment. Yet, despite the central role these genes and their restricted expression patterns play in Drosophila development, we still do not understand how these patterns are established or maintained. Here, by dissecting the regulatory sequences required for ap expression, we solve this problem for this critical selector gene. We used a combination of experimental approaches to identify and functionally characterize the cis-regulatory modules (CRMs) that regulate ap expression during Drosophila wing development. For these analyses we implement a novel technique allowing us to study the function of these CRMs in vivo, at the native ap locus. We found three ap CRMs crucial for wing development: the Early (apE) and the D/V (apDV) enhancers and the ap PRE (apP). Only when all three regulatory elements are combined is a uniform and complete ap expression domain generated. In summary, our results indicate that ap is regulated in time and space by a three-step mechanism that generates a lineage compartment by integrating input from separate CRMs for the initiation, refinement and maintenance of its expression.


Vyšlo v časopise: Establishment of a Developmental Compartment Requires Interactions between Three Synergistic -regulatory Modules. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005376
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005376

Souhrn

The separation of cell populations into distinct functional units is essential for both vertebrate and invertebrate animal development. A classical paradigm for this phenomenon is the establishment of developmental compartments during Drosophila wing development. These compartments depend on the restricted expression of two selector genes, engrailed in the posterior compartment and apterous (ap) in the dorsal compartment. Yet, despite the central role these genes and their restricted expression patterns play in Drosophila development, we still do not understand how these patterns are established or maintained. Here, by dissecting the regulatory sequences required for ap expression, we solve this problem for this critical selector gene. We used a combination of experimental approaches to identify and functionally characterize the cis-regulatory modules (CRMs) that regulate ap expression during Drosophila wing development. For these analyses we implement a novel technique allowing us to study the function of these CRMs in vivo, at the native ap locus. We found three ap CRMs crucial for wing development: the Early (apE) and the D/V (apDV) enhancers and the ap PRE (apP). Only when all three regulatory elements are combined is a uniform and complete ap expression domain generated. In summary, our results indicate that ap is regulated in time and space by a three-step mechanism that generates a lineage compartment by integrating input from separate CRMs for the initiation, refinement and maintenance of its expression.


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