Fetal and maternal asymmetry in plasma membrane domains of syncytiotrophoblast layer-I cells are maintained by a polarity-regulating factor

Research Project

Project/Area Number	17H06995
Research Category	Grant-in-Aid for Research Activity Start-up
Allocation Type	Single-year Grants
Research Field	Obstetrics and gynecology
Research Institution	Institute of Physical and Chemical Research (2018) Yokohama City University (2017)
Principal Investigator	Tamura Kana 国立研究開発法人理化学研究所, 生命機能科学研究センター, 研究員 (70807461)
Project Period (FY)	2017-08-25 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	胎盤 / aPKC / 合胞体栄養膜細胞 / 細胞極性 / YAP / 極性 / 栄養膜細胞
Outline of Final Research Achievements	The syncytiotrophoblast have the machinery for the exchange of specific substances between fetal and maternal blood and seems to serve as a barrier for the vectorial transport of these substances. However, how these proteins are asymmetrically localized between the maternal side and fetal side-membrane domain in syncytiotrophoblasts is unknown. One of the most conserved regulators of cellular asymmetry, cell polarity, is aPKC. KIBRA is the regulator of aPKC during epithelial polarization. In this study, focused on the KIBRA homolog, KIBRA-like/Wwc2 (KIBRAL). We produced KIBRAL knock-out (KO) mouse, and found that KIBRAL-KO mouse shows cell polarity defects in syncytiotrophoblast layer-I (SynT-I) cells. We demonstrated that SynT-I cells have unique cell polarity. Our results suggest that KIBRAL is required for proper localization of cellular machineries including nutrient transporters, which are essential for vectorial transport of substances between fetus and mother.
Academic Significance and Societal Importance of the Research Achievements	本研究により、胎盤の最大の機能である「母体と胎児の物質交換」に必須であるトランスポーターの位置決定機構の一端を明らかにした。本研究はマウス胎盤を用いたものだが、ヒト胎盤とマウス胎盤は構造が酷似している。したがって、Wwc2の遺伝子異常は、胎盤形成異常を介したヒト胎児発育不全を引き起こす原因の1つになり得るだろう。今後、新たな流産のリスク因子の1つとして、Wwc2が遺伝子検査の対象となる可能性が高いと考える。