Functional analysis of sphingosine-1-phosphate in hematopoietic development using genome editing technologies

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03681
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• Research Institution: University of Yamanashi
• Principal Investigator: KAWAHARA Atsuo 山梨大学, 大学院総合研究部, 教授 (10362518)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ゲノム編集技術 / TALEN / CRISPR/Cas9 / スフィンゴシン-1-リン酸 / S1P受容体 / Spns2

Outline of Final Research Achievements

The purpose of this study is to reveal the physiological function of the lipid mediator, sphingosine-1-phosphate (S1P) during zebrafish organogenesis. We have established exhaustive S1PR knockout fish mediated by genome editing technologies and investigated the phenotypic analyses of these mutants. 7S1PR mutant, which was disrupted in all S1PRs, exhibited embryonic lethal. 7S1PR mutant showed not only cardia bifida like S1PR2 mutant, but also hypoplasia of vascular and erythroid cells. These results indicate that S1P signal plays important roles in hematopoietic and vascular development.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

脂質メディエーターであるスフィンゴシン-1-リン酸(S1P)の生理機能は十分には分かっていない。本研究では、ゲノム編集技術を用い全てのS1PRを破壊したゼブラフィッシュ変異体の表現型解析から、S1Pシグナルが造血および心血管発生に重要な役割を担うことを明らかにした。哺乳類において本研究で解明されたS1Pの新機能が保存されているかを調べることで、S1Pシグナルの総括的な理解が深まることが期待される。