Siva plays a critical role in mouse embryonic development.

Cell Death Differ
Authors
Abstract

The Siva protein, named after the Hindu God of Destruction, plays important roles in apoptosis in various contexts, including downstream of death receptor activation or p53 tumor suppressor engagement. The function of Siva in organismal development and homeostasis, however, has remained uncharacterized. Here, we generate Siva knockout mice to characterize the physiological function of Siva in vivo. Interestingly, we find that Siva deficiency causes early embryonic lethality accompanied by multiple phenotypes, including developmental delay, abnormal neural tube closure, and defective placenta and yolk sac formation. Examination of Siva expression during embryogenesis shows that Siva is expressed in both embryonic and extra-embryonic tissues, including within the mesoderm, which may explain the vascular defects observed in the placenta and yolk sac. The embryonic phenotypes caused by Siva loss are not rescued by p53 deficiency, nor do they resemble those of p53 null embryos, suggesting that the embryonic function of Siva is not related to the p53 pathway. Moreover, loss of the Ripk3 necroptosis protein does not rescue the observed lethality or developmental defects, suggesting that Siva may play a non-apoptotic role in development. Collectively, these studies reveal a key role for Siva in proper embryonic development.

Year of Publication
2020
Journal
Cell Death Differ
Volume
27
Issue
1
Pages
297-309
Date Published
2020 Jan
ISSN
1476-5403
DOI
10.1038/s41418-019-0358-x
PubMed ID
31164717
PubMed Central ID
PMC7205994
Links
Grant list
F31 CA167917 / CA / NCI NIH HHS / United States
R35 CA197591 / CA / NCI NIH HHS / United States
1F31CA167917-01 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
5R03NS05618002 / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)