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

European Journal of Cell Biology
Preethi VijayarajT M Magin

Abstract

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.

References

Jul 1, 1993·Genes & Development·H BaribaultR G Oshima
Feb 1, 1995·Clinical Pharmacokinetics·P BourgetH Fernandez
Apr 29, 1998·The Journal of Cell Biology·H D GabrielK Willecke
Oct 13, 1998·Current Biology : CB·C V PepicelliA P McMahon
Jan 29, 1999·Physiological Reviews·C YeamanW J Nelson
Nov 4, 2000·The Journal of Cell Biology·Y TamaiM M Taketo
Apr 26, 2002·Cell Death and Differentiation·R G Oshima
May 29, 2003·The Journal of Cell Biology·Daniel JaquemarRobert G Oshima
Dec 10, 2003·Experimental Hematology·Margaret H Baron
Apr 17, 2004·European Journal of Cell Biology·Michael HesseThomas M Magin
Oct 12, 2004·Annual Review of Cell and Developmental Biology·Elena SanchoHans Clevers
Oct 27, 2004·Experimental Cell Research·Thomas M MaginMechthild Hatzfeld
Nov 13, 2004·The New England Journal of Medicine·M Bishr OmaryW H Irwin McLean
Nov 5, 2005·The EMBO Journal·Johanna IvaskaPeter J Parker
Jan 24, 2006·Nature Cell Biology·Mikko NieminenSirpa Jalkanen
Feb 9, 2006·American Journal of Human Genetics·Regina C BetzRoland Kruse
Jul 13, 2006·The Journal of Cell Biology·Jürgen SchweizerMathew W Wright
Feb 23, 2007·Nature·Elaine Fuchs
Apr 17, 2007·Experimental Cell Research·Thomas M MaginRudolf E Leube
Sep 21, 2007·Development·Jeanette Astorga, Peter Carlsson
May 14, 2008·The Journal of Cell Biology·Amanda E Bass-ZubekKathleen J Green
Oct 21, 2009·The Journal of Cell Biology·Preethi VijayarajThomas M Magin

❮ Previous
Next ❯

Citations

May 20, 2015·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Rebecca L TallmadgeM Julia B Felippe
Jun 19, 2012·The Biochemical Journal·Feride Oeztuerk-Winder, Juan-Jose Ventura
Mar 26, 2011·The American Journal of Pathology·Cornelia KrögerThomas M Magin
Nov 19, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marika SjöqvistCecilia Sahlgren

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.