Development of the mammalian axial skeleton requires signaling through the Gαi subfamily of heterotrimeric G proteins.
ABSTRACT 129/SvEv mice with a loss-of-function mutation in the heterotrimeric G protein α-subunit gene Gnai3 have fusions of ribs and lumbar vertebrae, indicating a requirement for Gα(i) (the "inhibitory" class of α-subunits) in somite derivatives. Mice with mutations of Gnai1 or Gnai2 have neither defect, but loss of both Gnai3 and one of the other two genes increases the number and severity of rib fusions without affecting the lumbar fusions. No myotome defects are observed in Gnai3/Gnai1 double-mutant embryos, and crosses with a conditional allele of Gnai2 indicate that Gα(i) is specifically required in cartilage precursors. Penetrance and expressivity of the rib fusion phenotype is altered in mice with a mixed C57BL/6 × 129/SvEv genetic background. These phenotypes reveal a previously unknown role for G protein-coupled signaling pathways in development of the axial skeleton.
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Dataset: 2014.Rashi et al.DinoTails
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ABSTRACT: A particularly critical event in avian evolution was the transition from long- to short-tailed birds. Primitive bird tails underwent significant alteration, most notably reduction of the number of caudal vertebrae and fusion of the distal caudal vertebrae into an ossified pygostyle. These changes, among others, occurred over a very short evolutionary interval, which brings into focus the underlying mechanisms behind those changes. Despite the wealth of studies delving into avian evolution, virtually nothing is understood about the genetic and developmental events responsible for the emergence of short, fused tails. In this review, we summarize the current understanding of the signaling pathways and morphological events that contribute to tail extension and termination and examine how mutations affecting the genes that control these pathways might influence the evolution of the avian tail. To generate a list of candidate genes that may have been modulated in the transition to short-tailed birds, we analyzed a comprehensive set of mouse mutants. Interestingly, a prevalent pleiotropic effect of mutations that cause fused caudal vertebral bodies (as in the pygostyles of birds) is tail truncation. We identified 23 mutations in this class, and these were primarily restricted to genes involved in axial extension. At least half of the mutations that cause short, fused tails lie in the Notch/Wnt pathway of somite boundary formation or differentiation, leading to changes in somite number or size. Several of the mutations also cause additional bone fusions in the trunk skeleton, reminiscent of those observed in primitive and modern birds. All of our findings were correlated to the fossil record. An open question is whether the relatively sudden appearance of short-tailed birds in the fossil record could be accounted for, at least in part, by the pleiotropic effects generated by a relatively small number of mutational events.EvoDevo 07/2014; 5(25):1-20. · 3.10 Impact Factor