title: The ALK-2 and ALK-4 activin receptors transduce distinct mesoderm-inducing signals during early Xenopus development but do not co-operate to establish thresholds.
abstract: The TGFbeta family member activin induces different mesodermal cell types in a dose-dependent fashion in the Xenopus animal cap assay. High concentrations of activin induce dorsal and anterior cell types such as notochord and muscle, while low concentrations induce ventral and posterior tissues such as mesenchyme and mesothelium. In this paper we investigate whether this threshold phenomenon involves the differential effects of the two type I activin receptors ALK-2 and ALK-4. Injection of RNA encoding constitutively active forms of the receptors (here designated ALK-2* and ALK-4*) reveals that ALK-4* strongly induces the more posterior mesodermal marker Xbra and the dorsoanterior marker goosecoid in animal cap explants. Maximal levels of Xbra expression are attained using lower concentrations of RNA than are required for the strongest activation of goosecoid, and at the highest doses of ALK-4*, levels of Xbra transcription decrease, as is seen with high concentrations of activin. By contrast, the ALK-2* receptor activates Xbra but fails to induce goosecoid to significant levels. Analysis at later stages reveals that ALK-4* signalling induces the formation of a variety of mesodermal derivatives, including dorsal cell types, in a dose-dependent fashion, and that high levels also induce endoderm. By contrast, the ALK-2* receptor induces only ventral mesodermal markers. Consistent with these observations, ALK-4* is capable of inducing a secondary axis when injected into the ventral side of 32-cell stage embryos whilst ALK-2* cannot. Co-injection of RNAs encoding constitutively active forms of both receptors reveals that ventralising signals from ALK-2* antagonise the dorsal mesoderm-inducing signal derived from ALK-4*, suggesting that the two receptors use distinct and interfering signalling pathways. Together, these results show that although ALK-2* and ALK-4* transduce distinct signals, the threshold responses characteristic of activin cannot be due to interactions between these two pathways; rather, thresholds can be established by ALK-4* alone. Furthermore, the effects of ALK-2* signalling are at odds with it behaving as an activin receptor in the early Xenopus embryo.
authors.affiliation: Division of Developmental Biology, National Institute for Medical Research, The Ridgeway, London, UK.
authors.forename: N A
authors.initials: NA
authors.lastname: Armes
authors.forename: J C
authors.initials: JC
authors.lastname: Smith
mesh_terms: D030201:Activin Receptors, Type I; D000818:Animals; D015415:Biomarkers; D019521:Body Patterning / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004625:Embryo, Nonmammalian / Q000502:physiology*; D004627:Embryonic Induction / Q000502:physiology*; D005326:Fetal Proteins / Q000096:biosynthesis; D018507:Gene Expression Regulation, Developmental; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D008648:Mesoderm / Q000166:cytology / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000096:biosynthesis / Q000502:physiology*; D012097:Repressor Proteins; D015398:Signal Transduction; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000096:biosynthesis; D014158:Transcription, Genetic; D014982:Xenopus laevis / Q000196:embryology*; D000098908:Brachyury Protein
chemical_list: D030201:Activin Receptors, Type I; D015415:Biomarkers; D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D017978:Receptors, Growth Factor; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D000098908:Brachyury Protein