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Evolutionarily conserved developmental pathways


Activin signaling pathway - Required in Drosophila in imaginal discs and brain and in vertebrates throughout development

Although there is compelling proof for the existence of invertebrate BMP-like signaling pathways, the evidence forinvertebrate TGF-beta or Activin-like signaling pathways has been scant. Baboon (Babo) is an invertebrate Activin type I receptor: the characterization of Baboon may well be the first evidence for the existence of an Activin-like signaling pathway in Drosophila. Null mutations and germ-line clonal analysis demonstrate that babo is not required during embryogenesis but is essential for proper pupation and adult viability. Loss of babo function results inlate larval or early pupal lethality. The major defect in these mutants is a reduction of cell proliferation within the primordia for adultstructures, specifically imaginal discs and brain tissue. Activated Babo can signal to vertebrateTGF-beta/Activin, but not to BMP-responsive promoters in cell culture. Activated Babo cannot bind to or interact withDrosophila Mad in tissue culture but can utilize a new Drosophila Smad homolog, dSmad2 (Smad on X), which relates most closely to the vertebrateSmads 2 and 3. Drosophila dSmad2 is highly expressed in tissues that require babo function and can be phosphorylated by eitheroverexpression of activated Babo or by overexpression of wild-type Punt and Babo together. On the basis of these results, it is proposedthat an Activin-like signaling pathway exists in Drosophila, which is required for proper cell proliferation in many primordial adult tissues (Brummel, 1999).

Smad2, whichis a tumor suppressor involved in colorectal and lung cancer, has been shown toinduce dorsal mesoderm in Xenopus laevis in response to transforming growthfactor beta and activins. The smad2 gene is expressed ubiquitously during murineembryogenesis and in many adult mouse tissues. Animals that lack smad2 diebefore 8.5 days of development (E8.5). E6.5 smad2homozygous mutants are smaller thancontrols, lack the extraembryonic portion of the egg cylinder, and appearstrikingly similar to E6.5 smad4 mutants. This similarity is no longer evidentat E7.5, however, because the smad2 mutants contained embryonic ectoderm withintheir interiors. Molecular analysis has shown that smad2 mutant embryos do notundergo gastrulation or make mesoderm. The results demonstrate that smad2 isrequired for egg cylinder elongation, gastrulation, and mesoderm induction (Weinstein, 1998).

Drosophila                  Homologs in other species ----------                  -------------------not yet characterized       Xenopus: Activin                            Mammals: Activin  Baboon                      Xenopus: ALK-2 and ALK-4                            Mammalian: ActRIA and ActRIBPunt                        Xenopus: XActRIIB                            Mammalian: ActRIIA and ActRIIBMedea                       C. elegans: Sma-4                            Xenopus: XSMad1                             Human: SMad4, also known as DPC4                        Smad on X                   C. elegans:  Sma-2 and Sma-3                            zebrafish: Smad2 and Smad3                            Human: Smad2 and Smad3

date revised: 30 September 2000

Developmental Pathways conserved in Evolution

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