Cropped, Drosophila transcription factor AP-4, controls tracheal terminal branching and cell growth

Abstract

BackgroundEndothelial or epithelial cellular branching is vital in development and cancer progression; however, the molecular mechanisms of these processes are not clear. In Drosophila, terminal cell at the end of some tracheal tube ramifies numerous fine branches on the internal organs to supply oxygen. To discover more genes involved in terminal branching, we searched for mutants with very few terminal branches using the Kiss enhancer-trap line collection.ResultsIn this analysis, we identified cropped (crp), encoding the Drosophila homolog of the transcription activator protein AP-4. Overexpressing the wild-type crp gene or a mutant that lacks the DNA-binding region in either the tracheal tissues or terminal cells led to a loss-of-function phenotype, implying that crp can affect terminal branching. Unexpectedly, the ectopic expression of cropped also led to enlarged organs, and cell-counting experiments on the salivary glands suggest that elevated levels of AP-4 increase cell size and organ size. Like its mammalian counterpart, cropped is controlled by dMyc, as ectopic expression of dMyc in terminal cells increased cellular branching and the Cropped protein levels in vivo.ConclusionsWe find that the branching morphogenesis of terminal cells of the tracheal tubes in Drosophila requires the dMyc-dependent activation of Cropped/AP-4 protein to increase the cell growth of terminal cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12861-015-0069-6) contains supplementary material, which is available to authorized users.

Comparative Transcriptomics in Two Extreme Neopterans Reveals General Trends in the Evolution of Modern Insects

“…In mid-late embryogenesis, lethal of scute , a gene involved in the neurogenesis and specification of sensory organs ( Negre and Simpson, 2015 ), is highly expressed in B. germanica , whereas shuttle craft , required to maintain the proper morphology of motoneuronal axon nerve routes ( Stroumbakis et al., 1996 ), is highly expressed in D. melanogaster . Also typical of late embryo stages of D. melanogaster is the high level of expression of little imaginal discs , a histone demethylase that specifically removes H3K4me3, a mark associated with active transcription ( Li et al., 2010 ), and cropped , a gene essential for embryonic tracheal terminal branching ( Wong et al., 2015 ). The aforementioned expression divergences refer to genes with no relevant roles in general patterning or organogenesis and could respond to circuitries specific of B. germanica and D. melanogaster , rather than being considered as reflecting general trends of evolution of development.…”

ARE-mediated decay controls gene expression and cellular metabolism upon oxygen variations

“…This subgroup of transcripts also includes branchless (bnl) and cropped (crp) which play major roles in the morphogenesis of the tracheal (respiratory) system (Fig. 3e ) 53 , 54 . Of note, bnl is transcriptionally controlled by HIF 55 and was previously identified as a target of dTIS11 21 .…”

Transcription Factor AP4 Mediates Cell Fate Decisions: To Divide, Age, or Die

“…Similarly, in Drosophila , d-Myc regulates AP4 homolog Cropped ( crp ) to control the development of the terminal branching of Drosophila tracheal tubes and cell size. In addition, overexpression of crp results in increased cell size and nuclear size [ 29 ], which may presumably be due to endoreplication, a process similar to the cell cycle without cytokinesis.…”

“…Similarly, in Drosophila, d-Myc regulates AP4 homolog Cropped (crp) to control the development of the terminal branching of Drosophila tracheal tubes and cell size. In addition, overexpression of crp results in increased cell size and nuclear size [29], which may presumably be due to endoreplication, a process similar to the cell cycle without cytokinesis. Among all human AP4 controlled genes, the cell cycle regulatory genes and the apoptosis genes were enriched in a Gene Ontology (GO) analysis, suggesting that AP4 regulates cell proliferation and death [3].…”