BIOLOGICAL OVERVIEW

All the genes involved in the activation of Torso and its targets make up the so-called terminal group. The synergistic network of interactions and influences involving these genes is known as the terminal pathway. The existence of a terminal pathway was discovered by analysis of mutations that delete both anterior and posterior embryonic structures. This pathway activates genes at both the anterior and posterior axis of the embryo.

Activation of the downstream targets of Torso involves a phosphorylation cascade. Upstream, a protein molecule (ligand), probably Trunk, triggers Torso signaling locally.

torso is the membrane receptor responsible for gene activation in the anterior and posterior ends of the embryo. Since the receptor Torso is uniformly distributed throughout the embryo, its activation must by necessity be local. The targets of Torso are members of the Ras pathway. The first target is the kinase D-raf, which in turn acts upon Ras1. Ras-1 is a docking protein that attaches itself to the cytoplasmic tails of receptors, which in their turn activate downstream targets. The resultant phosphorylation cascade activates tailless and huckebein, two targets of the terminal system. tailless is held in a state of repression by grainyhead/NTF-1 until Torso pathway signals inactivate the repression (Liaw, 1995).

Activation of Torso at the poles of the embryo triggers expression of the terminal zygotic gap genes tailless (tll) and huckebein (hkb). Tailless acts as a repressor of Kruppel and knirps in the central domain of the recently fertilized embryo. Groucho acts throughout the embryo to repress the repressor of Kruppel and knirps, allowing the expression of these gap genes in the central domain of the embryo. Patterning of the non-segmental termini of the Drosophila embryo depends on signaling via the Torso receptor tyrosine kinase. The Gro corepressor acts in this process to confine terminal gap gene expression to the embryonic termini. Embryos lacking maternal gro activity display ectopic tll and hkb transcription; in turn, tll then leads to lack of abdominal expression of the Kruppel and knirps gap genes. torso signaling permits terminal gap gene expression by antagonizing Gro-mediated repression. Groucho-mediated repression of tailless is relieved by the torso pathway suggesting that Groucho is the nuclear target for MAP kinase signaling. It is suggested that Groucho functions as a corepressor along with an unknown protein unrelated to Hairy, since Groucho mediated repression takes place in the absence of known Hairy-related bHLH proteins (Paroush, 1997).

The Torso pathway interacts with Dorsal. DL is phosphorylated through the Torso pathway and thus converted to a repressor (Ronchi, 1993). Torso pathway signals, possibly acting directly on target genes, mask the ability of DL to repress gene expression (Rusch, 1994). The Torso pathway also acts through homeotic genes to regulate proliferating cell nuclear antigen, thus regulating the cell cycle (Yamaguchi, 1995). A possible target of Torso pathway regulated transcription may be Raf (Sprenger, 1993).

The most likely candidate for Torso's ligand is Trunk. Trunk is distributed uniformly through the embryo and is presumably secreted and activated locally. Torso-like has been considered a potential ligand. It is made by follicle cells at either end of the egg. Perhaps Torso-like is part of a cascade for local activation of the Torso ligand (Martin, 1994 and Casanova, 1995).

GENE STRUCTURE

Exons - at least 13

PROTEIN STRUCTURE

Amino Acids - 923

Structural Domains

Torso has structural similarities to growth-factor receptor tyrosine kinases except that the extracellular domain does not resemble that of other known receptor tyrosine kinases. Torso has 12 potential extracellular glycosylation sites, a central transmembrane domain and two putative intracellular kinase domains (Sprenger, 1989).

EVOLUTIONARY HOMOLOGS

Insect axis formation is best understood in Drosophila, where rapid anteroposterior patterning of zygotic determinants is directed by maternal gene products. The earliest zygotic control is by gap genes, which determine regions of several contiguous segments and are largely conserved in insects. Isolation of mutations has been used to approach a genetic question: do early zygotic patterning genes control similar anteroposterior domains in the parasitoid wasp Nasonia vitripennis as in Drosophila? Nasonia is advantageous for identifying and studying recessive zygotic lethal mutations because unfertilized eggs develop as males while fertilized eggs develop as females. On first consideration, the Hymenopteran Nasonia and the Dipteran Drosophila appear very similar in their embryonic development, though the Hymenoptera diverged from the Diptera >200 million years ago. Embryos of both species produce larvae in about 1 day at 25°C. In Nasonia, the fertilized egg gives rise to an embryo that undergoes syncytial and cellular blastoderm stages morphologically similar to those of Drosophila. Both Nasonia and Drosophila undergo the long germband mode of embryonic development. Despite these similarities, two observations suggest that the relative importance of maternal versus zygotic patterning functions may differ in the two insects. (1) Although postgastrulation events proceed with very similar timing, the time for early development differs substantially - at 25°C: the events preceding gastrulation take only about 3 hours in Drosophila but almost 10 hours in Nasonia. This difference in timing may allow for greater zygotic control of patterning in Nasonia than in Drosophila. (2) Among the relatives of Nasonia, a polyembryonic mode of development has evolved in which a single fertilized egg gives rise to hundreds or thousands of progeny. Polyembryonic development is likely to rely heavily on zygotic control of patterning. Polyembryony has arisen several times in the Hymenoptera, and the polyembryonic Copidosoma floridanum is in the same superfamily as Nasonia. These considerations pose the following question -- is early development substantially controlled by the zygotic genome in Hymenopterans? This question may be approached genetically, by isolating zygotic mutations that disrupt early anteroposterior patterning in Nasonia. Recessive zygotic mutations have identified three Nasonia genes: head only mutant embryos have posterior defects, resembling loss of both maternal and zygotic Drosophila caudal function; headless mutant embryos have anterior and posterior gap defects, resembling loss of both maternal and zygotic Drosophila hunchback function, and squiggy mutant embryos develop only four full trunk segments, a phenotype more severe than those caused by lack of Drosophila maternal or zygotic terminal gene functions. head only mutant embryos lack all segmentation posterior to the head, in the strongest manifestation of the phenotype, and have only a narrow domain of Ubx-Abd-A expression. head only differs from Drosophila gap genes with respect to the extent of pattern deleted and effects on Ubx-Abd-A. In Drosophila, neither Krüppel nor knirps affects a domain as large as that of head only. Moreover, the wild-type functions of Krüppel and knirps are not required for the positive regulation of Ubx or abd-A in Drosophila (Pultz, 1999).

squiggy mutant embryos have severe defects both anteriorly and posteriorly, leaving only four consistently developed trunk segments. This cuticular phenotype differs substantially from the phenotypes of maternal terminal group genes in Drosophila, such as torso, in which loss-of-function maternal-effect mutations delete pattern elements from both ends of the embryo. The terminal structures deleted in torso embryos are anterior to the gnathal segments and posterior to the seventh abdominal segment, and are thus limited compared to those of the zygotic squiggy mutant embryos. The extensive zygotic control of terminal development by squiggy appears to be a departure from Drosophila developmental mechanisms. The Drosophila maternal terminal gene patterning system is not known to be widely conserved, and the follicle cell types that express torsolike do not appear to be conserved even in the lower Diptera. Terminal patterning in insects may therefore be subject to considerable evolutionary flexibility. Zygotic control of early patterning in head only, headless and squiggy mutants share a common theme: the zygotic Nasonia phenotypes are more extreme than those of Drosophila gap genes and all three genes appear to control processes zygotically that are partially or fully subject to maternal control in the fly. These results indicate greater dependence on the zygotic genome to control early patterning in Nasonia than in the fly (Pultz, 1999).

date revised: 10 March 99

Home page: The Interactive Fly © 1995, 1996 Thomas B. Brody, Ph.D.