Positional information provided solely by the mother is sufficient to subdivide the Drosophila embryo into three domains (ventral, lateral, and dorsal) corresponding to three basic tissue types (mesoderm, neuroectoderm, and non-neural ectoderm). Ovarian follicle cells collaborate with the oocyte to activate an extracellular complement-related protease cascade culminating in the production of a ventral signal called Spätzle. The Spätzle signal generates a nuclear concentration gradient of the NFk-B-related Dorsal transcription factor in the responding embryo. Nuclear Dorsal levels are high in ventral presumptive mesodermal cells, lower in lateral cells comprising the neuroectoderm, and absent in cells giving rise to non-neural ectoderm (Fig. 1).
Once in the nucleus, maternal Dorsal determines D/V domains of zygotic gene expression in a concentration dependent fashion (Fig. 1). Dorsal functions as an activator of genes expressed in ventral and lateral regions of the embryo, but as a repressor of genes expressed in dorsal cells. In ventral cells, the mesoderm determining genes twist and snail are activated by peak levels of Dorsal. Lower levels of Dorsal activate expression of rhomboid (rho) in lateral presumptive neuroectodermal cells. Similarly, lateral expression of short gastrulation (sog) is dependent on Dorsal, although it remains to determined whether this effect is due to direct activation. A cluster of related bHLH encoding genes comprising the achaete-scute Complex (AS-C) are also expressed in lateral cells. Dorsal, however, is not an essential activator of these genes. Cells of the dorsal non-neural ectoderm have undetectable levels of nuclear Dorsal, which permits the expression of several genes including decapentaplegic (dpp), zerknüllt (zen), and tolloid (tld). In ventral and lateral cells, Dorsal represses expression of these target genes.
While the mother is responsible for determining the position of lateral neuroectoderm versus dorsal non-neural ectoderm in Drosophila, zygotic genes expressed in each of these domains are required to maintain that initial subdivision. Two genes which play a pivotal role in the neural versus non-neural subdivision of the ectoderm are sog and dpp. dpp is expressed in dorsal non-neural cells and encodes a secreted TGF-ß family member (Dpp) most related to the vertebrate bone morphogenetic protein-4 (BMP-4), while sog is expressed in the neuroectoderm and encodes a predicted extracellular protein (Sog) similar to vertebrate Chordin (Chd) (François et al., 1994; François and Bier, 1995). Both Dpp and Sog are likely to diffuse from their sites of production into adjacent territories. As discussed on the Dpp-Sog page, Dpp and Sog are expressed in the same relative patterns as BMP-4 and Chd respectively, and these homologous pairs of molecules are functionally interchangeable between flies and frogs (François and Bier, 1995; Schmidt et al., 1995).
sog and dpp function antagonistically several times during Drosophila embryogenesis (François et al., 1994; Biehs et al., 1996) and pupal development (Yu et al., 1996). In the early blastoderm embryo, sog opposes dpp in two different contexts: 1) Sog prevents Dpp signaling from invading the neuroectoderm, and 2) Sog is required for subdividing the dorsal region into amnioserosa (the dorsal-most domain) and dorsal non-neural ectoderm, most likely by creating a Dpp activity gradient (Biehs et al., 1996).
In the early embryo, Dpp signaling functions both to maintain expression of dorsally-acting genes and to suppress expression of neuroectodermal genes (Biehs et al., 1996). Several dorsally-acting genes are transcriptionally activated by Dpp signaling including zen and dpp itself. The positive feedback loop through which Dpp signaling activates its own expression is referred to as autoactivation (Fig. 2). Among the genes repressed by Dpp signaling are those of the AS-Complex, which provide a necessary pre-condition for neural development. Because AS-C genes can be expressed dorsally in the absence of Dpp and nuclear Dorsal, Dorsal plays little, if any, role in restricting AS-C expression to lateral cells. Expression of AS-C in the absence of Dorsal is consistent with the formation of cuticle having partial neuroectodermal character in dpp dl double mutant embryos. Thus, Dpp signaling simultaneously promotes dorsal non-neural ectodermal cell fates while it suppresses neuroectodermal fates.
As the mother initially restricts dpp expression to dorsal cells through the repressive action of Dorsal, one could ask why it should be necessary to have a Dpp antagonist such as Sog in the neuroectoderm? The reason is schematically represented in Figs. 1. and 2. Dpp protein produced in dorsal cells diffuses down into the neuroectoderm where it can autoactivate to induce de novo dpp expression. This results in an invasive positive feedback loop (i.e. Dpp diffuses into the non-dpp expressing domain and activates dpp expression in those cells). Dpp diffusion and autoactivation are useful properties for assuring that all cells within the dorsal domain assume a non-neural fate. However, active opposition of Dpp signaling within the neuroectoderm is necessary to prevent dpp expression from spreading throughout the entire ectoderm.
