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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 for invertebrate 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 in late larval or early pupal lethality. The major defect in these mutants is a reduction of cell proliferation within the primordia for adult structures, specifically imaginal discs and brain tissue. Activated Babo can signal to vertebrate TGF-beta/Activin, but not to BMP-responsive promoters in cell culture. Activated Babo cannot bind to or interact with Drosophila Mad in tissue culture but can utilize a new Drosophila Smad homolog, dSmad2 (Smad on X), which relates most closely to the vertebrate Smads 2 and 3. Drosophila dSmad2 is highly expressed in tissues that require babo function and can be phosphorylated by either overexpression of activated Babo or by overexpression of wild-type Punt and Babo together. On the basis of these results, it is proposed that an Activin-like signaling pathway exists in Drosophila, which is required for proper cell proliferation in many primordial adult tissues (Brummel, 1999).

Smad2, which is a tumor suppressor involved in colorectal and lung cancer, has been shown to induce dorsal mesoderm in Xenopus laevis in response to transforming growth factor beta and activins. The smad2 gene is expressed ubiquitously during murine embryogenesis and in many adult mouse tissues. Animals that lack smad2 die before 8.5 days of development (E8.5). E6.5 smad2homozygous mutants are smaller than controls, lack the extraembryonic portion of the egg cylinder, and appear strikingly similar to E6.5 smad4 mutants. This similarity is no longer evident at E7.5, however, because the smad2 mutants contained embryonic ectoderm within their interiors. Molecular analysis has shown that smad2 mutant embryos do not undergo gastrulation or make mesoderm. The results demonstrate that smad2 is required 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 ActRIB

Punt                        Xenopus: XActRIIB
                            Mammalian: ActRIIA and ActRIIB

Medea                       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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