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XB-ART-46591
Development. March 1, 2013; 140 (5): 976-86.

Lin28 proteins are required for germ layer specification in Xenopus.

Faas L , Warrander FC , Maguire R , Ramsbottom SA , Quinn D , Genever P , Isaacs HV .


Abstract
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.

PubMed ID: 23344711
Article link: Development.
Grant support: BB/H000925/1 Biotechnology and Biological Sciences Research Council

Genes referenced: chrd.1 fgf4 fgf8 gapdh grin1 lin28a lin28b mcf2 myod1 nodal nodal5 nodal6 odc1 smad2 sst t

Antibodies referenced: Lin28a Ab2 Lin28b Ab1
Morpholinos referenced: lin28a MO1 lin28a MO2 lin28b MO1


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