The Drosophila short gastrulation gene prevents Dpp from autoactivating and suppressing neurogenesis in the neuroectoderm.

Abstract

The short gastrulation (sog) gene is expressed in broad lateral stripes comprising the neuroectoderm of the Drosophila blastoderm embryo, sog encodes a predicted secreted protein that functions nonautonomously to antagonize the activity of the TGF-~-like Decapentaplegic (Dpp) signaling pathway in the dorsal region of the embryo. Recently, it has been shown that sog and dpp are functionally equivalent to their respective Xenopus homologs chordin and BMP-4. In this report we provide the first direct evidence that sog plays a local role in the lateral region of the blastoderm embryo to oppose Dpp activity in the neuroectoderm. In the dorsal region, Dpp signaling both suppresses neurogenesis and maintains expression of genes that promote dorsal cell fates (dorsalization). We show that Dpp also can perform both of these functions in the neuroectoderm. In wild-type embryos, the ability of Dpp to induce expression of dorsal markers including itself (autoactivation) in the neuroectoderm is blocked by sog. We propose that Sog protects the neuroectoderm from an invasive positive feedback loop created by Dpp diffusion and autoactivation. We show that the two functions of Dpp signaling, neural suppression and dorsalization, are triggered by distinct thresholds of Dpp activity. Epistasis experiments reveal that all observed sog activity can be accounted for by Sog functioning as a dedicated Dpp antagonist. Finally, we provide evidence that Sog functions as a diffusible morphogen in the blastoderm embryo. These data strongly support the view that the primary phylogenetically conserved function of the Drosophila sog and dpp genes and the homologous Xenopus chordin and BMP-4 genes is to subdivide the primitive embryonic ectoderm into neural versus non-neural domains.

Model Organisms in the Study of Development and Disease

“…Scw appears to function in more of a helper capacity, however, since elevating Dpp levels can rescue scw mutants (Arora et al, 1994). BMP signaling plays two roles in specifying the nonneural ectoderm: it activates expression of genes required for dorsal cell fates, such as zen (Ray et al, 1991), and it suppresses expression of neural genes Biehs et al, 1996;von Ohlen and Doe, 2000). One of the genes activated by BMP signaling is dpp itself, which results in a positive feedback autoactivation loop (Biehs et al, 1996).…”

“…As described in more detail below, a variety of evidence suggests that Dpp acts in a dose-dependent fashion to specify at least two different dorsal cell fates (Ferguson and Anderson, 1992a, b;Wharton et al, 1993;Biehs et al, 1996;Jazwinska et al, 1999b). In this model, peak Dpp activity specifies the dorsalmost cell type (amnioserosa), while lower levels of Dpp signaling specify dorsal nonneural ectoderm.…”

“…Cell dissociation and reaggregation experiments using Xenopus ectoderm revealed that BMP4 signaling actively suppresses a default preference of vertebrate ectodermal cells to become neural Wilson and Hemmati-Brivanlou, 1995) and that neural inducers such as Chordin and Noggin function by inhibiting this negative action of BMP4 signaling (reviewed in Hemmati-Brivanlou and Melton, 1997). Likewise, in Drosophila embryos, several neural genes, including the critical neural promoting genes of the ASC, are ectopically expressed in dpp Ϫ mutant embryos (Biehs et al, 1996), while ectopic Dpp expression suppresses expression of neural genes in the neuroectoderm. In genetically sensitized sog Ϫ mutant embryos, the autoactivating function of BMP signaling can lead to the spread of dpp expression into the neuroectoderm, which then activates expression of Dpp targets and represses expression of neural genes (Biehs et al, 1996).…”

“…As in the case of the mesoderm, repression also plays an important role in establishing the neural ectoderm since mutations in the repressor brk result in ectopic expression of dorsal ectodermal genes, such as dpp laterally (Jazwinska et al, 1999b;Rushlow et al, 2001;Zhang et al, 2001). Sog encodes a secreted antagonist of bone morphogenetic protein (BMP; see Chapter 24) signaling (Francois et al, 1994) and acts in parallel with brk to prevent BMP signaling from spreading into the neuroectoderm (Biehs et al, 1996). Sog blocks the activity of the BMP Screw (Scw) (Neul and Ferguson, 1998;Nguyen et al, 1998), which is expressed ubiquitously in the early embryo and acts in concert with Dpp to define peak levels of BMP signaling (Arora et al, 1994).…”

“…Sog blocks the activity of the BMP Screw (Scw) (Neul and Ferguson, 1998;Nguyen et al, 1998), which is expressed ubiquitously in the early embryo and acts in concert with Dpp to define peak levels of BMP signaling (Arora et al, 1994). By blocking Scw, Sog interferes with an invasive positive feedback loop of BMP signaling created by Dpp diffusing laterally and activating its own expression in the neuroectoderm (Biehs et al, 1996;Bier, 1997). As discussed further below, this interplay between Sog and Dpp is important for the primary subdivision of the ectoderm into neural versus nonneural domains and has been highly conserved during the course of evolution (Bier, 1997).…”