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XB-ART-36203
Proc Natl Acad Sci U S A July 17, 2007; 104 (29): 12029-34.
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Vertebrate Ctr1 coordinates morphogenesis and progenitor cell fate and regulates embryonic stem cell differentiation.

Haremaki T , Fraser ST , Kuo YM , Baron MH , Weinstein DC .


Abstract
Embryogenesis involves two distinct processes. On the one hand, cells must specialize, acquiring fates appropriate to their positions (differentiation); on the other hand, they must physically construct the embryo through coordinated mechanical activity (morphogenesis). In early vertebrate development, fibroblast growth factor (FGF) regulates multiple embryonic events, including germ layer differentiation and morphogenesis; the cellular components that direct FGF signaling to evoke these different responses remain largely unknown. We show here that the copper transporter 1 (Ctr1) protein is a critical router of FGF signals during early embryogenesis. Ctr1 both promotes the differentiation and inhibits the morphogenesis of mesoderm and neurectoderm in embryos of the frog Xenopus laevis, thereby coordinating normal development. Signal sorting by Ctr1 involves the activation of the Ras-MAP kinase cascade and appears to be independent of its role in copper transport. Mouse embryonic stem (ES) cells deficient for Ctr1 (Ctr1(-/-)) retain characteristics of pluripotency under conditions that favor differentiation in wild-type ES cells, indicating a conserved role for Ctr1 during amphibian and mammalian cell fate determination. Our studies support a model in which vertebrate Ctr1 functions as a key regulator of the differentiation capacity of both stem and progenitor cell populations.

PubMed ID: 17620605
PMC ID: PMC1924542
Article link: Proc Natl Acad Sci U S A
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: acta4 actc1 actl6a cdx4 dvl2 frs2 gal.2 hck kdr kit lif mapk1 myc ncam1 nrp1 otx2 slc31a1 sox2 tbxt
Antibodies: Kdr Ab2 Neuronal Ab5 Somite Ab1
Morpholinos: slc31a1 MO1


Article Images: [+] show captions
References [+] :
Aller, Projection structure of the human copper transporter CTR1 at 6-A resolution reveals a compact trimer with a novel channel-like architecture. 2006, Pubmed