An orphan gene is necessary for preaxial digit formation during salamander limb development.
Limb development in salamanders differs from other tetrapods in that the first digits to form are the two most anterior (preaxial dominance). This has been proposed as a salamander novelty and its mechanistic basis is unknown. Salamanders are the only adult tetrapods able to regenerate the limb, and the contribution of preaxial dominance to limb regeneration is unclear. Here we show that during early outgrowth of the limb bud, a small cohort of cells express the orphan gene Prod1 together with Bmp2, a critical player in digit condensation in amniotes. Disruption of Prod1 with a gene-editing nuclease abrogates these cells, and blocks formation of the radius and ulna, and outgrowth of the anterior digits. Preaxial dominance is a notable feature of limb regeneration in the larval newt, but this changes abruptly after metamorphosis so that the formation of anterior and posterior digits occurs together within the autopodium resembling an amniote-like pattern.
Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E 6BT, UK.
Anoop
A
Kumar
Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E 6BT, UK.
Phillip B
PB
Gates
Department of Genetics, Evolution and Environment, Division of Biosciences, University College London, London WC1E 6BT, UK.
Anna
A
Czarkwiani
Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E 6BT, UK.
Jeremy P
JP
Brockes
D029845:Amphibian Proteins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D005121:Extremities / Q000254:growth & development* / Q000502:physiology; D005260:Female; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D008297:Male; D038081:Organogenesis; D057093:Orphan Nuclear Receptors / Q000235:genetics* / Q000378:metabolism; D012038:Regeneration; D014562:Caudata / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism
D029845:Amphibian Proteins; D057093:Orphan Nuclear Receptors