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Visceral endoderm function is regulated by quaking and required for vascular development
Author(s) -
Bohnsack Brenda L.,
Lai Lihua,
Northrop Jennifer L.,
Justice Monica J.,
Hirschi Karen K.
Publication year - 2006
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/gene.20189
Subject(s) - endoderm , biology , mutant , gene isoform , microbiology and biotechnology , alternative splicing , embryonic stem cell , genetics , gene
The quaking (qkI) gene produces three major alternatively spliced variants ( qkI‐5,‐6,‐7) that encode for proteins that share the RNA binding, KH domain. Previous studies utilizing the qk k2 allele, which contains an N‐ethyl‐N‐nitrosourea (ENU)‐induced point mutation in the KH domain, demonstrate that this functional region of qkI is required for embryonic vascular development. In the current studies we demonstrate that qk l‐1 /qk l‐1 mutants, which lack the QKI‐5 splice variant, also died at midgestation due to vascular remodeling defects. In addition, although all three QKI isoforms were expressed in the visceral endoderm of wildtype yolk sacs, qkI‐6 and qkI‐7 transcript and protein expression were suppressed in qk k2 /qk k2 and qk l‐1 /qk l‐1 mutant yolk sacs, suggesting that the KH‐domain of QKI‐5 was required for qkI‐6 and qkI‐7 expression. Further studies revealed that the cellular role of qkI is to regulate visceral endoderm function, including the local synthesis of retinoic acid (RA) and the subsequent control of endothelial cell proliferation, matrix production, and visceral endoderm survival. Although these defects were rescued by exogenous RA, visceral endoderm function or vascular remodeling were not restored. Thus, we conclude that qkI regulates visceral endoderm function, which is critical for vascular remodeling. genesis 44:93–104, 2006. © 2006 Wiley‐Liss, Inc.