Cause and stereo cilia function analysis of congenital hearing loss induced by LATS1 kinase deficiency.

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K18744
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Keio University
• Principal Investigator: Nishiyama Takanori 慶應義塾大学, 医学部(信濃町), 講師 (90627168)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: LATS1 / Hippo経路 / 内耳

Outline of Final Research Achievements

The Hippo pathway is an intracellular signalling pathway that regulates the cell cycle and defines tissue size and morphology. LATS1/2 kinases are molecules that maintain the cell skeleton, of which only LATS1 is found in the organ of Corti, and deficiency of LATS1 causes congenital inner ear hair cell damage. The pathology of congenital cochlear deafness is caused by the irregular allignment of inner and outer hair cells due to LATS1 deficiency, indicating that LATS1 is an essential protein during the development of inner ear anatomies. On the other hand, hetero mice were found to be devoid of such a condition.

Free Research Field

耳科

Academic Significance and Societal Importance of the Research Achievements

Hippo経路は、その破綻による細胞周期調節経路の異常と細胞の腫瘍化の関連が大きく注目されており、LATS1を含むHippo経路の構成因子を腫瘍治療の標的にした研究が多く行われている。今回の我々の研究は、Hippo経路の重要な構成因子であるLATS1の働きが失われることで、内耳有毛細胞の発生に異常を来たす事が分かった。この成果はLATS1が担っている新たな機能に関する報告であり、内耳研究だけでなくHippo経路に関わる研究に対する新たな知見として貢献した。