TY - JOUR
T1 - Pias1 is essential for erythroid and vascular development in the mouse embryo
AU - Constanzo, Jerfiz D.
AU - Deng Ph.D., Mi
AU - Rindhe, Smita
AU - Tang, Ke jing
AU - Zhang, Chengcheng
AU - Scaglioni, Pier P
N1 - Funding Information:
We thank Lisa Sowels and Margherita Melegari, for administrative assistance and the transgenic technology center at UT Southwestern for ES cell injections. We would also like to thank Dr. Hongtao Yu, Dr. Jerry W. Shay, Dr. Rolf Brekken and Dr. Mariya Ilcheva for helpful discussion and for reviewing this research manuscript. In addition, we like to thank Dr. Ondine Cleaver for constructive comments of the manuscript and sharing the Tie2 +/Cre mice. This work was supported by NCI, United States Grant #1F31CA180689-01 (to JDC), NIH, United States grants #1R01CA137195 , UT Southwestern Friends of the Comprehensive Cancer Center , Texas 4000 (to PPS), #1R01CA172268 (to CCZ) and the Harold C. Simmons Cancer Center through NCI, United States Cancer Center support Grant 2P30CA016672 .
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - The protein inhibitor of activated STAT-1 (PIAS1) is one of the few known SUMO E3 ligases. PIAS1 has been implicated in several biological processes including repression of innate immunity and DNA repair. However, PIAS1 function during development and tissue differentiation has not been studied. Here, we report that Pias1 is required for proper embryonic development. Approximately 90% of Pias1 null embryos die in utero between E10.5 and E12.5. We found significant apoptosis within the yolk sac (YS) blood vessels and concomitant loss of red blood cells (RBCs) resulting in profound anemia. In addition, Pias1 loss impairs YS angiogenesis and results in defective capillary plexus formation and blood vessel occlusions. Moreover, heart development is impaired as a result of loss of myocardium muscle mass. Accordingly, we found that Pias1 expression in primary myoblasts enhances the induction of cardiac muscle genes MyoD, Myogenin and Myomaker. PIAS1 protein regulation of cardiac gene transcription is dependent on transcription factors Myocardin and Gata-4. Finally, endothelial cell specific inactivation of Pias1 in vivo impairs YS erythrogenesis, angiogenesis and recapitulates loss of myocardium muscle mass. However, these defects are not sufficient to recapitulate the lethal phenotype of Pias1 null embryos. These findings highlight Pias1 as an essential gene for YS erythropoiesis and vasculogenesis in vivo.
AB - The protein inhibitor of activated STAT-1 (PIAS1) is one of the few known SUMO E3 ligases. PIAS1 has been implicated in several biological processes including repression of innate immunity and DNA repair. However, PIAS1 function during development and tissue differentiation has not been studied. Here, we report that Pias1 is required for proper embryonic development. Approximately 90% of Pias1 null embryos die in utero between E10.5 and E12.5. We found significant apoptosis within the yolk sac (YS) blood vessels and concomitant loss of red blood cells (RBCs) resulting in profound anemia. In addition, Pias1 loss impairs YS angiogenesis and results in defective capillary plexus formation and blood vessel occlusions. Moreover, heart development is impaired as a result of loss of myocardium muscle mass. Accordingly, we found that Pias1 expression in primary myoblasts enhances the induction of cardiac muscle genes MyoD, Myogenin and Myomaker. PIAS1 protein regulation of cardiac gene transcription is dependent on transcription factors Myocardin and Gata-4. Finally, endothelial cell specific inactivation of Pias1 in vivo impairs YS erythrogenesis, angiogenesis and recapitulates loss of myocardium muscle mass. However, these defects are not sufficient to recapitulate the lethal phenotype of Pias1 null embryos. These findings highlight Pias1 as an essential gene for YS erythropoiesis and vasculogenesis in vivo.
KW - Angiogenesis
KW - Embryonic development
KW - Fetal erythropoiesis
KW - Pias1
KW - Yolk sac capillary plexus
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U2 - 10.1016/j.ydbio.2016.04.013
DO - 10.1016/j.ydbio.2016.04.013
M3 - Article
C2 - 27155222
AN - SCOPUS:84969549231
VL - 415
SP - 98
EP - 110
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 1
ER -