Cell Fate Specification in theDrosophilaSalivary Gland: The Integration of Homeotic Gene Function with the DPP Signaling Cascade

Abstract

Salivary gland formation in the Drosophila embryo is linked to the expression of the homeotic gene Sex combs reduced (Scr). When Scr function is missing, salivary glands do not form, and when SCR is expressed everywhere, salivary glands form in new places. However, not every cell that expresses Scr is recruited to a salivary gland fate. Along the anterior-posterior axis, the posteriorly expressed proteins encoded by the teashirt (tsh) and Abdominal-B (Abd-B) genes block SCR activation of salivary gland genes, and along the dorsal-ventral axis, the secreted signaling molecule encoded by decapentaplegic (dpp) prevents activation of salivary gland genes by SCR in dorsal regions of parasegment 2. We have identified five downstream components in the DPP signaling cascade required to block salivary gland gene activation. These components include two known receptors, the type I receptor encoded by the thick veins (tkv) gene and the type II receptor encoded by the punt (put) gene; two of the four known Drosophila members of the Smad family of proteins which transduce signals from the receptors to the nucleus, Mothers against dpp (Mad) and Medea (Med); and, finally, a large zinc-finger transcription factor encoded by the schnurri (shn) gene. These results reveal how anterior-posterior and dorsal-ventral patterning information is integrated at the level of organ-specific gene expression.

A Zinc Finger Transcription Factor, αA-Crystallin Binding Protein 1, Is a Negative Regulator of the Chondrocyte-Specific Enhancer of the α1(II) Collagen Gene

“…Recent studies demonstrated the possible involvement of Schnurri and SEM-4 in the growth factor signaling pathway and mesoderm development. Schnurri is shown to be necessary for the signaling pathway of Drosophila decapentaplegic, a member of the transforming growth factor ␤ superfamily most closely related to the vertebrate bone morphogenetic proteins BMP-2 and BMP-4 (2,15,17). Genetic analysis using C. elegans has demonstrated that SEM-4 is required for the development of neuronal cells and mesodermal cell lineage (4,8).…”

Organ-specific gene expression: the bHLH protein Sage provides tissue specificity toDrosophilaFoxA

“…7). At the top of the hierarchy are the genes that regulate the decision to form SGs: Scr-Exd-Hth, in the absence of the negative regulators Dpp, Tsh and Abd-B (Panzer et al, 1992;Henderson et al, 1999;Henderson and Andrew, 2000). ScrExd-Hth activate expression of CrebA, Sage, Fkh and Hkb, which function to maintain and implement the SG fate decision by maintaining their own expression, the expression of each other and of terminally differentiated gene products.…”

“…SGs are initially specified by the combined activities of the homeotic protein Sex combs reduced (Scr) and its co-factors Extradenticle (Exd) and Homothorax (Hth) (Panzer et al, 1992;Ryoo and Mann, 1999;Henderson and Andrew, 2000). All three factors are essential for SG formation and ectopic expression of Scr, the one spatially limited component, can induce SG cell fates in the subset of ectodermal cells that do not experience activated Dpp signaling (dorsal cells) or express neither Teashirt (Tsh) (parasegments 3-14) or Abdominal B (Abd-B) (parasegment 15) (Panzer et al, 1992;Henderson et al, 1999). In the SG secretory cells, Scr and its co-factors activate the expression of several transcription factors, including Fkh, the bZip protein CrebA, the bHLH protein Sage and the SP1-like protein Huckebein (Hkb) (Panzer et al, 1992;Andrew et al, 1997;Myat and Andrew, 2000b).…”

Zinc‐finger paralogues tsh and tio are functionally equivalent during imaginal development in Drosophila and maintain their expression levels through auto‐ and cross‐negative feedback loops

“…During embryogenesis, tsh has been shown to participate in the patterning of the epidermis (Fasano et al, 1991;Roder et al, 1992;Andrew et al, 1994;de Zulueta et al, 1994;Gallet et al, 1998Gallet et al, , 2000Robertson et al, 2004) and the development of the salivary glands (Henderson et al, 1999) and the gut (Mathies et al, 1994;Waltzer et al, 2001;Saller et al, 2002), and tsh null mutants are embryonic lethal (Fasano et al, 1991). The Drosophila genome contains also a tsh paralogue, tiptop (tio; Laugier et al, 2005).…”