pannierandpointedP2act sequentially to regulateDrosophilaheart development

Abstract

The Drosophila heart consists of two major cell types: cardioblasts, which form the contractile tube of the heart; and pericardial cells, which flank the cardioblasts and are thought to filter and detoxify the blood or hemolymph of the fly. We present the completion of the entire cell lineage of all heart cells. Notably, we detect a previously unappreciated distinction between the lineages of heart cells located in the posterior seven segments relative to those located more anteriorly. Using a genetic screen, we have identified the ETS-transcription factor pointed as a key regulator of cardioblast and pericardial cell fates in the posterior seven segments of the heart. In this domain, pointed promotes pericardial cell development and opposes cardioblast development. We find that this function of pointed is carried out primarily if not exclusively by the pointedP2 isoform and, that in this context, pointedP2 may act independently of Ras/MAPK pathway activity. We go on to show that the GATA transcription factor pannier acts early in dorsal mesoderm development to promote the development of the cardiac mesoderm and thus all heart cells. Finally, we demonstrate that pannier acts upstream of pointed in a developmental pathway in which pannier promotes cardiac mesoderm formation, and pointed acts subsequently in this domain to distinguish between cardioblast and pericardial cell fates.

Downstream of Homeotic Genes: In the Heart of Hox function

“…40 A recent report suggests that lymph gland cells could share a common progenitor with thoracic CMs, 54 contradicting previous observations. 32,47 The fact that Antp misexpression represses lymph gland development without modifying cardiac cell lineage strongly supports the idea that lymphoid and cardiac organs do not share a common origin. Moreover, the shared effect of Antp, Ubx and abdA overexpression on lymph gland development might point out an early common property of at least these three Hox genes in repressing lymph gland development.…”

“…1A and B and D-D"). [32][33][34] At stage 13, cardiac cells undergo a mesenchyme/ epithelium transition 35 to form two continuous rows of cells, one on each side of the embryo. These two rows of epithelial cells, associated with the PCs, migrate towards the dorsal midline during dorsal closure (stage 14/15).…”

“…38,39 Laterally, these CMs are flanked by the lymph glands, the larval hematopoietic organ, identified by the presence of the Odd-skipped (Odd) transcription factor 34 and the lack of the type IV collagen protein Pericardin (Prc). 36 Ventrally and dorsally, thoracic CMs are flanked by six pairs of PCs, which are all prc-expressing but not odd-expressing cells (the majority of them express Tin, two pairs also co-express Tin and Even skipped (Eve); 32,40 Fig. 1D').…”

“…1D' and D"). 32,34,47 Given that one aspect of the axial distribution of the cardiac and associated cell types correlates with the particular domains of Hox expression, we and others investigated the involvement of Hox genes in the generation of cardiac cell diversity. 40,[43][44][45][46]48 Removal of the five Hox genes Scr, Antp, Ubx, abdA and AbdB yields a complete transformation of all abdominal segments into thoracic ones, based on the number of CMs, on CM subtypes, as well as on number and type of associated PCs.…”

Cellular components and signals required for the cardiac outflow tract assembly in Drosophila

“…A broad amount of data has been generated based on this assumption, revealing that although structurally simple, the Drosophila heart is composed of discrete subsets of cardioblasts and pericardial cells, making it more complex than previously thought (3)(4)(5). Both cell types can be subdivided into subpopulations expressing a cell subset-specific combinatorial code of transcription factors (6)(7)(8)(9)(10)(11)(12)(13). Such a subdivision suggests that different subsets of cardiac cells differentiate into functionally distinct heart components-a possibility that is supported by the finding that the Svp/Doc-positive pair of cardioblasts has the capacity to develop into the inflow tract (ostial) cells (9,14), whereas the four Tin-expressing cardioblasts adopt a cell fate of ''working myocardium'' (15).…”