Date Published: June 3, 2019
Publisher: Public Library of Science
Author(s): Candice V. Lovato, TyAnna L. Lovato, Richard M. Cripps, Barbara Jennings.
Understanding the transcriptional pathways controlling tissue-specific gene expression is critical to unraveling the complex regulatory networks that underlie developmental mechanisms. Here, we assessed how the Drosophila crossveinless (cv) gene, that encodes a BMP-binding factor, is transcriptionally regulated in the developing embryonic tracheal system. We identify an upstream regulatory region of cv that promotes reporter gene expression in the tracheal precursors. We further demonstrate that this promoter region is directly responsive to the basic, helix-loop-helix-PAS domain factors Trachealess (Trh) and Tango (Tgo), that function to specify tracheal fate. Moreover, cv expression in embryos is lost in trh mutants, and the integrity of the Trh/Tgo binding sites are required for promoter-lacZ expression. These findings for the first time elucidate the transcriptional regulation of one member of a family of BMP binding proteins, that have diverse functions in animal development.
It is now readily established that conserved transcriptional networks form the basis of developmental pathways, to shape tissues and organs in developing animals. Understanding the relationships between regulatory factors and their target genes is critical to defining these transcriptional networks. Moreover, familiarity with the genetic programs controlling normal development provides insight into how development goes awry in the diseased state.
In this manuscript, we set out to define how cv transcription is activated in the Drosophila embryo, and we found that this occurs through the combined activities of Trh and Tgo. These bHLH-PAS domain transcription factors bind to the cv promoter region, and positively impact cv expression. Previous studies have established that cv is expressed in tracheal precursor cells [15,16], yet this is the first study to assess how expression of cv is controlled. Our data and conclusions are therefore of interest for a number of reasons. Firstly, cv encodes a cysteine-rich protein and a member of a conserved family of molecules that function to modulate BMP signaling (reviewed in ). Relatively little is known of how the expression of cv-like genes is controlled in any organism; therefore our studies, implicating the conserved PAS domain proteins Trh and Tgo, provide new insight into the regulation of the gene family that has the potential to be of broad relevance.