Lin28 proteins are required for germ layer specification in Xenopus.
Lin28 family proteins share a unique structure, with both zinc knuckle and cold shock RNA-binding domains, and were originally identified as regulators of developmental timing in Caenorhabditis elegans. They have since been implicated as regulators of pluripotency in mammalian stem cells in culture. Using Xenopus tropicalis, we have undertaken the first analysis of the effects on the early development of a vertebrate embryo resulting from global inhibition of the Lin28 family. The Xenopus genome contains two Lin28-related genes, lin28a and lin28b. lin28a is expressed zygotically, whereas lin28b is expressed both zygotically and maternally. Both lin28a and lin28b are expressed in pluripotent cells of the Xenopus embryo and are enriched in cells that respond to mesoderm-inducing signals. The development of axial and paraxial mesoderm is severely abnormal in lin28 knockdown (morphant) embryos. In culture, the ability of pluripotent cells from the embryo to respond to the FGF and activin/nodal-like mesoderm-inducing pathways is compromised following inhibition of lin28 function. Furthermore, there are complex effects on the temporal regulation of, and the responses to, mesoderm-inducing signals in lin28 morphant embryos. We provide evidence that Xenopus lin28 proteins play a key role in choreographing the responses of pluripotent cells in the early embryo to the signals that regulate germ layer specification, and that this early function is probably independent of the recognised role of Lin28 proteins in negatively regulating let-7 miRNA biogenesis.
Area 11, Department of Biology, University of York, York, YO10 5DD, UK.
Laura
L
Faas
Fiona C
FC
Warrander
Richard
R
Maguire
Simon A
SA
Ramsbottom
Diana
D
Quinn
Paul
P
Genever
Harry V
HV
Isaacs
D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D003001:Cloning, Molecular; D004625:Embryo, Nonmammalian; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005855:Germ Layers / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D060172:Morpholinos / Q000494:pharmacology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014018:Tissue Distribution / Q000187:drug effects; D014981:Xenopus / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C579731:Lin28a protein, Xenopus; D060172:Morpholinos; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D029867:Xenopus Proteins; D005346:Fibroblast Growth Factors