Figure 2.

BMP signaling in Drosophila dorsal-ventral patterning. (a) Molecular-level events in BMP signaling at the dorsal surface of the Drosophila embryo. BMP ligands consist of homodimers of either Dpp or Scw or a heterodimer of Dpp and Scw. These ligands (generically represented with gray coloring) form ternary complexes with the proteins Sog and Tsg, which prevents binding of these ligands to their receptors. Tolloid (Tld), a metalloprotease, degrades Sog, the loss of which promotes dissociation of the complex and liberation of the BMP ligand and Tsg. Free Dpp can bind the type II receptor, Punt, and its type I receptor, Tkv, whereas Scw binds to Punt and another type I receptor, Sax. The active type I receptors within the receptor complex phosphorylate the Drosophila Smad1 homolog, Mad. Phospho-Mad forms a complex with the Smad4 homolog, Medea. The phospho-Mad-Medea complex shuttles into the nucleus and regulates the transcription of target genes. (b) Sites of production of the BMP ligands and putative extracellular modulators of BMP signaling. Represented is a transverse cross-section of the Drosophila embryo. Dpp, Scw, Tld, and Tsg are broadly expressed in the dorsal region whereas Sog is expressed ventro-laterally [53]. In the dorsal region, BMP receptors and Mad are expressed uniformly [53]. (c). A simplified view of the dynamics of the extracellular events in BMP signaling (for simplicity, only Dpp is only shown). Solid arrows indicate biochemical reactions, broken arrows represent transport by diffusion. The basic mechanism operates as follows: Dpp diffuses down its concentration gradient ventro-laterally (i); Sog counteracts the movement of Dpp by binding to it and diffusing down its own concentration gradient (ii and iii) transporting Dpp dorsally (iv). Tsg facilitates complex formation between Sog and Dpp. Tld cleaves Sog, which liberates Dpp and Tsg from the complex (v) so that Dpp is free to bind its receptors to initiate signaling (vi). Degradation of Sog by Tld also provides a ‘sink’ for Sog that maintains its concentration gradient. The net result is a sharp phospho-Mad (P-Mad) gradient and downstream signaling in cells located near the dorsal midline.