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Publication : Keratins regulate yolk sac hematopoiesis and vasculogenesis through reduced BMP-4 signaling.

First Author  Vijayaraj P Year  2010
Journal  Eur J Cell Biol Volume  89
Issue  4 Pages  299-306
PubMed ID  20097443 Mgi Jnum  J:305685
Mgi Id  MGI:6705258 Doi  10.1016/j.ejcb.2009.10.016
Citation  Vijayaraj P, et al. (2010) Keratins regulate yolk sac hematopoiesis and vasculogenesis through reduced BMP-4 signaling. Eur J Cell Biol 89(4):299-306
abstractText  Keratin intermediate filament proteins form the major cytoskeleton in all embryonic and adult epithelia. Increasing evidence suggests that keratins, besides their primary cytoskeletal function, can act as scaffolds which locally regulate cell growth and survival in epithelial cells. Many of these functions, however, are not understood in full, owing to keratin redundancy. We have recently created mice which lack all keratins and found that keratins act upstream of mTOR signaling to regulate protein biosynthesis via GLUT localization. Here, we report that keratins are necessary to maintain adhesion between endodermal and mesodermal cell layers of the yolk sac. As a consequence, keratin(-/-) embryos suffer from reduced yolk sac hematopoiesis and vasculogenesis. Pathway analysis revealed a reduction of the hedgehog target Foxf1 in yolk sac mesoderm of keratin(-/-) embryos, and subsequent reduction of BMP-4 and P-p38 MAPK. These defects may be caused by the overall reduction in protein biosynthesis and diminished adhesion. Our data show for the first time that keratins are necessary for the differentiation of a non-epithelial cell lineage through a combination of mechanical and signaling mechanisms.
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