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Phenotypic variation is a prerequisite for evolution by natural selection, yet the processes that give rise to the novel morphologies upon which selection acts are poorly understood. We employed a chemical genetic screen to identify developmental changes capable of generating ecologically relevant morphological variation as observed among extant species. Specifically, we assayed for exogenously applied small molecules capable of transforming the ancestral larval foregut of the herbivorous Xenopus laevis to resemble the derived larval foregut of the carnivorous Lepidobatrachus laevis. Appropriately, the small molecules that demonstrate this capacity modulate conserved morphogenetic pathways involved in gut development, including downregulation of retinoic acid (RA) signaling. Identical manipulation of RA signaling in a species that is more closely related to Lepidobatrachus, Ceratophrys cranwelli, yielded even more similar transformations, corroborating the relevance of RA signaling variation in interspecific morphological change. Finally, we were able to recover the ancestral gut phenotype in Lepidobatrachus by performing a reverse chemical manipulation to upregulate RA signaling, providing strong evidence that modifications to this specific pathway promoted the emergence of a lineage-specific phenotypic novelty. Interestingly, our screen also revealed pathways that have not yet been implicated in early gut morphogenesis, such as thyroid hormone signaling. In general, the chemical genetic screen may be a valuable tool for identifying developmental mechanisms that underlie ecologically and evolutionarily relevant phenotypic variation.
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???displayArticle.pmcLink???PMC3870478 ???displayArticle.link???Evol Dev ???displayArticle.grants???[+]
Abzhanov,
Bmp4 and morphological variation of beaks in Darwin's finches.
2004, Pubmed
Abzhanov,
Bmp4 and morphological variation of beaks in Darwin's finches.
2004,
Pubmed
Banker,
Thyroid hormone receptor can modulate retinoic acid-mediated axis formation in frog embryogenesis.
1993,
Pubmed
,
Xenbase
Blomhoff,
Overview of retinoid metabolism and function.
2006,
Pubmed
Campione,
The homeobox gene Pitx2: mediator of asymmetric left-right signaling in vertebrate heart and gut looping.
1999,
Pubmed
,
Xenbase
Carroll,
Gastric Pepsin in an Anuran Larva: (Lepidobatrachus laevis/pepsinogen).
1991,
Pubmed
Carroll,
Evo-devo and an expanding evolutionary synthesis: a genetic theory of morphological evolution.
2008,
Pubmed
Chalmers,
Development of the gut in Xenopus laevis.
1998,
Pubmed
,
Xenbase
Chalmers,
The Xenopus tadpole gut: fate maps and morphogenetic movements.
2000,
Pubmed
,
Xenbase
Chazaud,
Retinoic acid is required in the mouse embryo for left-right asymmetry determination and heart morphogenesis.
1999,
Pubmed
,
Xenbase
Dush,
Heterotaxin: a TGF-β signaling inhibitor identified in a multi-phenotype profiling screen in Xenopus embryos.
2011,
Pubmed
,
Xenbase
Gilbert,
The morphogenesis of evolutionary developmental biology.
2003,
Pubmed
Hasebe,
Thyroid hormone-up-regulated hedgehog interacting protein is involved in larval-to-adult intestinal remodeling by regulating sonic hedgehog signaling pathway in Xenopus laevis.
2008,
Pubmed
,
Xenbase
Holtfreter,
[Not Available].
1931,
Pubmed
Ishizuya-Oka,
Thyroid hormone-induced apoptosis of larval cells and differentiation of pepsinogen-producing cells in the stomach of Xenopus laevis in vitro.
1998,
Pubmed
,
Xenbase
Ishizuya-Oka,
Thyroid hormone-induced expression of sonic hedgehog correlates with adult epithelial development during remodeling of the Xenopus stomach and intestine.
2001,
Pubmed
,
Xenbase
Itasaki,
Changes in the arrangement of actin bundles during heart looping in the chick embryo.
1989,
Pubmed
Itasaki,
Actin bundles on the right side in the caudal part of the heart tube play a role in dextro-looping in the embryonic chick heart.
1991,
Pubmed
Keidel,
Different agonist- and antagonist-induced conformational changes in retinoic acid receptors analyzed by protease mapping.
1994,
Pubmed
Kopp,
Drosophila sex combs as a model of evolutionary innovations.
2011,
Pubmed
Kopp,
Genetic control and evolution of sexually dimorphic characters in Drosophila.
2000,
Pubmed
Latacha,
Role of actin polymerization in bending of the early heart tube.
2005,
Pubmed
Laudet,
The origins and evolution of vertebrate metamorphosis.
2011,
Pubmed
,
Xenbase
Lipscomb,
Role for retinoid signaling in left-right asymmetric digestive organ morphogenesis.
2006,
Pubmed
,
Xenbase
Logan,
The transcription factor Pitx2 mediates situs-specific morphogenesis in response to left-right asymmetric signals.
1998,
Pubmed
Matt,
Retinoic acid-dependent eye morphogenesis is orchestrated by neural crest cells.
2005,
Pubmed
Matt,
Impairing retinoic acid signalling in the neural crest cells is sufficient to alter entire eye morphogenesis.
2008,
Pubmed
Moczek,
Emerging model systems in evo-devo: horned beetles and the origins of diversity.
2007,
Pubmed
Moczek,
The role of developmental plasticity in evolutionary innovation.
2011,
Pubmed
Mukhi,
Remodeling the exocrine pancreas at metamorphosis in Xenopus laevis.
2008,
Pubmed
,
Xenbase
Muller,
Left-right asymmetric morphogenesis in the Xenopus digestive system.
2003,
Pubmed
,
Xenbase
Pearl,
Xenopus pancreas development.
2009,
Pubmed
,
Xenbase
Pryor,
Symbiotic fermentation, digesta passage, and gastrointestinal morphology in bullfrog tadpoles (Rana catesbeiana).
2005,
Pubmed
Ramasubramanian,
Computational model for early cardiac looping.
2006,
Pubmed
Ridley,
Life at the leading edge.
2011,
Pubmed
Rowe,
Retinoid X receptors.
1997,
Pubmed
Ryan,
Pitx2 determines left-right asymmetry of internal organs in vertebrates.
1998,
Pubmed
,
Xenbase
Ryan,
Hedgehog secretion and signal transduction in vertebrates.
2012,
Pubmed
Schreiber,
Remodeling of the intestine during metamorphosis of Xenopus laevis.
2005,
Pubmed
,
Xenbase
Schweickert,
Pitx2 isoforms: involvement of Pitx2c but not Pitx2a or Pitx2b in vertebrate left-right asymmetry.
2000,
Pubmed
,
Xenbase
Shapiro,
Genetic and developmental basis of evolutionary pelvic reduction in threespine sticklebacks.
2004,
Pubmed
Smith,
Evolutionary relationships between the amphibian, avian, and mammalian stomachs.
2000,
Pubmed
,
Xenbase
Stockwell,
Chemical genetics: ligand-based discovery of gene function.
2000,
Pubmed
Stolow,
Xenopus sonic hedgehog as a potential morphogen during embryogenesis and thyroid hormone-dependent metamorphosis.
1995,
Pubmed
,
Xenbase
TAHARA,
Topography of the presumptive rudiments in the endoderm of the anuran neurula.
1961,
Pubmed
Tehrani,
Endocrine pancreas development in zebrafish.
2011,
Pubmed
True,
Developmental system drift and flexibility in evolutionary trajectories.
2001,
Pubmed
Tsukui,
Multiple left-right asymmetry defects in Shh(-/-) mutant mice unveil a convergence of the shh and retinoic acid pathways in the control of Lefty-1.
1999,
Pubmed
Wheeler,
Xenopus: an ideal system for chemical genetics.
2012,
Pubmed
,
Xenbase
Wheeler,
Simple vertebrate models for chemical genetics and drug discovery screens: lessons from zebrafish and Xenopus.
2009,
Pubmed
,
Xenbase
Wild,
Description of the chondrocranium and osteogenesis of the Chacoan burrowing frog, Chacophrys pierotti (Anura: Leptodactylidae).
1999,
Pubmed
Wray,
The evolutionary significance of cis-regulatory mutations.
2007,
Pubmed
Yarmola,
Actin-latrunculin A structure and function. Differential modulation of actin-binding protein function by latrunculin A.
2000,
Pubmed