Whereas the mechanisms of early Drosophila mesoderm formation have been studied in much detail, the subsequent processes determining regional identities within the mesoderm remain largely unknown. Here, we describe two homeo box genes, tinman (tin) and bagpipe (bap), which spatially subdivide the mesoderm and determine cell fates in the dorsal mesoderm. These two genes are components of a cascade of genetic interactions that result in the spatial restriction of tin mRNA to the dorsal mesoderm and in the activation of bap in segmental clusters of cells in this region. A subset of cells from those clusters segregate to form visceral mesoderm that differentiates into gut musculature. This indicates that the visceral mesoderm is derived from metamerically repeated primordia. In embryos mutant for bap, visceral mesoderm formation is strongly disrupted. Most cells of the visceral mesoderm fail to differentiate properly, and a portion of them are transformed into body wall musculature and gonadal mesoderm. In tin mutant embryos, bap expression is not activated in the dorsal mesoderm. Probably as a consequence, neither visceral mesoderm nor midgut musculature are formed in these mutants, and the absence of visceral mesoderm results in strong disruptions of endoderm migration and midgut morphogenesis. In addition to visceral mesoderm development, tin is required for the formation of the heart from dorsal mesoderm and for the specification of founder cells for particular body wall muscles.

We have examined the position-dependent expression of two segmentation genes that contain a homeo box, even-skipped (eve) and fushi tarazu (ftz). Products encoded by both genes accumulate in a series of seven transverse stripes along the anterior-posterior body axis of developing embryos. Double-staining experiments show that eve and ftz proteins accumulate in complementary sets of embryonic cells. A total of eight zygotically active segmentation genes are required for the establishment and refinement of the eve and ftz expression patterns during development. Mutations that affect one of the genes were always found to produce a reciprocal alteration in the other. These results suggest that the eve and ftz promoters independently "interpret" the same positional cues to give differential patterns of expression. We propose that a combination of segmentation gene products that activates the expression of eve represses the expression of ftz, and vice versa. This proposal is discussed in the context of a hierarchy of interactions among segmentation genes, whereby the gap genes establish asymmetric patterns of eve and ftz expression in blastoderm-stage embryos, and interactions with other pair-rule genes serve to refine further the complementarity of eve and ftz expression during gastrulation and germ band elongation.

The heart is the first organ to form during embryogenesis and its circulatory function is critical from early on for the viability of the mammalian embryo. Developmental abnormalities of the heart have also been widely recognized as the underlying cause of many congenital heart malformations. Hence, the developmental mechanisms that orchestrate the formation and morphogenesis of this organ have received much attention among classical and molecular embryologists. Due to the evolutionary conservation of many of these processes, major insights have been gained from the studies of a number of vertebrate and invertebrate models, including mouse, chick, amphibians, zebrafish, and Drosophila . In all of these systems, the heart precursors are generated within bilateral fields in the lateral mesoderm and then converge toward the midline to form a beating linear heart tube. The specification of heart precursors is a result of multiple tissue and cell-cell interactions that involve temporally and spatially integrated programs of inductive signaling events. In the present review, we focus on the molecular and developmental functions of signaling processes during early cardiogenesis that have been defined in both vertebrate and invertebrate models. We discuss the current knowledge on the mechanisms through which signals induce the expression of cardiogenic transcription factors and the relationships between signaling pathways and transcriptional regulators that cooperate to control cardiac induction and the formation of a linear heart tube.

Dorsal mesoderm induction in arthropods and ventral mesoderm induction in vertebrates are closely related processes that involve signals of the BMP family. In Drosophila, induction of visceral mesoderm, dorsal muscles, and the heart by Dpp is, at least in part, effected through the transcriptional activation and function of the homeobox gene tinman in dorsal mesodermal cells during early embryogenesis. Here we present a functional dissection of atinman enhancer that mediates the Dpp response. We provide evidence that mesoderm-specific induction of tinman requires the binding of both activators and repressors. Screens for binding factors yielded Tinman itself and the Smad4 homolog Medea. We show that the binding and synergistic activities of Smad and Tinman proteins are critical for mesodermal tinman induction, whereas repressor binding sites prevent induction in the dorsal ectoderm and amnioserosa. Thus, integration of positive and negative regulators on enhancers of target genes appears to be an important mechanism in tissue-specific induction by TGF-β molecules.