Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Sep 1;9(9):a022152.
doi: 10.1101/cshperspect.a022152.

TGF-β Family Signaling in Drosophila

Ambuj Upadhyay  1 , Lindsay Moss-Taylor  1 , Myung-Jun Kim  1 , Arpan C Ghosh  1 , Michael B O'Connor  1
Affiliations
Review

TGF-β Family Signaling in Drosophila

Ambuj Upadhyay et al. Cold Spring Harb Perspect Biol. .

Erratum in

  • Erratum: TGF-β Family Signaling in Drosophila.
    Upadhyay A, Moss-Taylor L, Kim MJ, Ghosh AC, O'Connor MB. Upadhyay A, et al. Cold Spring Harb Perspect Biol. 2017 Mar 1;9(3):a031963. doi: 10.1101/cshperspect.a031963. Cold Spring Harb Perspect Biol. 2017. PMID: 28249961 Free PMC article. No abstract available.

Abstract

The transforming growth factor β (TGF-β) family signaling pathway is conserved and ubiquitous in animals. In Drosophila, fewer representatives of each signaling component are present compared with vertebrates, simplifying mechanistic study of the pathway. Although there are fewer family members, the TGF-β family pathway still regulates multiple and diverse functions in Drosophila. In this review, we focus our attention on several of the classic and best-studied functions for TGF-β family signaling in regulating Drosophila developmental processes such as embryonic and imaginal disc patterning, but we also describe several recently discovered roles in regulating hormonal, physiological, neuronal, innate immunity, and tissue homeostatic processes.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Core transforming growth factor β (TGF-β) family signaling components in Drosophila. Activin branch: Three ligands signal through the activin-specific type I receptor Babo. Each ligand is thought to have a dedicated receptor isoform, although evidence for Actβ-BaboB is lacking. Ligand binding induces formation of a receptor complex of both Babo and either of the type II receptors, Punt or Wishful thinking (Wit). Constitutively active type II receptors phosphorylate Babo, which activates dSmad2. Phosphorylated dSmad2 binds to Medea and translocates to the nucleus to regulate the transcriptional response. Bone morphogenetic protein (BMP) branch: Four ligands signal through shared the BMP-specific type I receptors Tkv and Sax and either Punt or Wit. The ligands are thought to primarily form homodimers, but there is one example of a heterodimer: Dpp–Scw. Mav is a divergent ligand based on sequence, but signals to activate Mad. Activation of type II receptors causes phosphorylation of type I receptors and subsequent phosphorylation of Mad, which then complexes with Medea to regulate transcription. In the absence of dSmad2, Babo can phosphorylate Mad and can also activate the Mad transcriptional response. Myo, Myoglianin; Actβ, Activin-β; Daw, Dawdle; Babo, Baboon; Mav, Maverick; Gbb, Glass-bottom boat; Dpp, Decapentaplegic; Scw, Screw; Sax, Saxophone; Tkv, Thickveins; Wit, Wishful thinking.
Figure 2.
Figure 2.
Drosophila embryo patterning. Wider distribution of pMad (early blastoderm) is converted to a restricted pMad stripe (late blastoderm) through the action of Sog, Tsg, and Tld. The combined activities of these factors result in net flux of the Dpp–Scw heterodimer to the dorsal midline. Homodimers stay broadly distributed as a result of low affinity to Sog.
Figure 3.
Figure 3.
Dpp signaling during Drosophila wing development. (A) During larval development, dpp (blue, top) is expressed along the A/P border and its gene product spreads to both compartments (blue arrows). High Dpp signaling in the middle of the disc results in activation of Mad (blue, below), which silences brk (red). The inverse gradients of pMad and Brk form the nested expression pattern of sal and omb. pMad is slightly lower in cells abutting the A/P axis due to local tkv down-regulation (Funakoshi et al. 2001). (B) Posterior crossvein (PCV) forms between the L4 and L5 veins (top), which begins during pupal development. Dpp–Gbb heterodimers bound by Sog (purple) and crossvein (dark green) allow for facilitated diffusion of ligands into the presumptive PCV space. Tolloid-related (Tlr) cleaves Sog and allows for signaling to occur. The initial broad signaling induces expression of CV-2, which further sharpens the signaling, resulting in PCV formation.
Figure 4.
Figure 4.
Bone morphogenetic protein (BMP) and activin signaling at the Drosophila neuromuscular junction (NMJ). Motor neuron-released Actβ induces Babo-mediated activation of dSmad2, facilitating association with Medea in the muscle. The pdSmad2-Medea complex then activates the transcription of glurIIB and an unknown factor(s) that controls posttranscriptional processing or mRNA stability of glurIIA. On the other hand, muscle-released Gbb binds Wit and the Tkv-Sax complex in the motor neuron, and stimulates Mad phosphorylation. The resultant pMad–Medea complex activates the transcription of trio and twit whose products promote synaptic growth and control spontaneous vesicle release, respectively. The expression of Gbb in the muscle is fine-tuned by glia-released Mav. The dotted lines in this model depict speculations that should be verified in future studies.
Figure 5.
Figure 5.
Bone morphogenetic protein (BMP) signaling in Drosophila female and male germline. (A) Schematic of the role of BMP signaling in the Drosophila female germline. BMP signaling mediated by Dpp released from the TF and cap cells regulates germinal stem cell (GSC) identity by inhibiting bam expression. (B) Schematic of the role of BMP signaling in Drosophila male germline. BMP ligands Dpp and Gbb released from the hub cells form a morphogen gradient that determines the number of transient amplifications the spermatogonia undergoes before differentiating into sperm. TF, Terminal filament cell; CB, cystoblast.
Figure 6.
Figure 6.
Dpp signaling in Drosophila gut. Schematic of the Drosophila midgut. dpp-Gal4-driven expression of GFP reveals two clusters of dpp expressing cells in the midgut, at the junction of the middle midgut (MM) and near the posterior end of the posterior midgut (PM). The expression of dpp from the first cluster of cells was shown to be necessary for specification of the copper cells and establishment of the copper cell region (CCR). A–C show the three proposed models of where dpp is expressed and released, and how Dpp regulates intestinal stem cell (ISC) proliferation and renewal. The validity of any of these models remains to be supported by additional studies. (A) Dpp released from the visceral muscle (orange) contains enterocyte (EC) cell injury-induced proliferation of ISCs. (B) Dpp released from trachea indirectly inhibits ISC proliferation by protecting the loss of EC cells. (C) Dpp released from the ECs acts as an autocrine signal to inhibit EC signals that induce ISC proliferation.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aberle H, Haghighi AP, Fetter RD, McCabe BD, Magalhães TR, Goodman CS. 2002. wishful thinking encodes a BMP type II Receptor that regulates synaptic growth in Drosophila. Neuron 33: 545–558. - PubMed
    1. Affolter M, Basler K. 2007. The decapentaplegic morphogen gradient: From pattern formation to growth regulation. Nat Rev Genet 8: 663–674. - PubMed
    1. Akiyama T, Gibson MC. 2015. Decapentaplegic and growth control in the developing Drosophila wing. Nature 527: 375–378. - PubMed
    1. Akiyama T, Kamimura K, Firkus C, Takeo S, Shimmi O, Nakato H. 2008. Dally regulates Dpp morphogen gradient formation by stabilizing Dpp on the cell surface. Dev Biol 313: 408–419. - PMC - PubMed
    1. Akiyama T, Marques G, Wharton KA. 2012. A large bioactive BMP ligand with distinct signaling properties is produced by alternative proconvertase processing. Sci Signal 5: ra28. - PMC - PubMed

MeSH terms

Substances

LinkOut - more resources

-