Mesd encodes an LRP5/6 chaperone essential for specification of mouse embryonic polarity.
Specification of embryonic polarity and pattern formation in multicellular organisms requires inductive signals from neighboring cells. One approach toward understanding these interactions is to study mutations that disrupt development. Here, we demonstrate that mesd, a gene identified in the mesoderm development (mesd) deletion interval on mouse chromosome 7, is essential for specification of embryonic polarity and mesoderm induction. MESD functions in the endoplasmic reticulum as a specific chaperone for LRP5 and LRP6, which in conjunction with Frizzled, are coreceptors for canonical WNT signal transduction. Disruption of embryonic polarity and mesoderm differentiation in mesd-deficient embryos likely results from a primary defect in WNT signaling. However, phenotypic differences between mesd-deficient and wnt3(-)(/)(-) embryos suggest that MESD may function on related members of the low-density lipoprotein receptor (LDLR) family, whose members mediate diverse cellular processes ranging from cargo transport to signaling.
Hsieh
Jen-Chih
JC
Department of Biochemistry and Cell Biology, Center for Developmental Genetics, State University of New York, Stony Brook, Stony Brook, NY 11794, USA.
Lee
Lance
L
Zhang
Liqun
L
Wefer
Stephen
S
Brown
Kristen
K
DeRossi
Charles
C
Wines
Mary E
ME
Rosenquist
Thomas
T
Holdener
Bernadette C
BC
D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D019556:COS Cells; D002454:Cell Differentiation / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics*; D000013:Congenital Abnormalities / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D005260:Female; D005804:Genes, Lethal / Q000235:genetics; D026502:LDL-Receptor Related Proteins; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D051153:Wnt Proteins; D060508:Wnt3 Protein
D026502:LDL-Receptor Related Proteins; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C555483:Lrp5 protein, mouse; C555476:Lrp6 protein, mouse; C472170:MESD protein, mouse; D018832:Molecular Chaperones; D011506:Proteins; D011973:Receptors, LDL; D051153:Wnt Proteins; D060508:Wnt3 Protein; C555508:Wnt3 protein, mouse