Inactivation of Lats1 and Lats2 highlights the role of hippo pathway effector YAP in larynx and vocal fold epithelium morphogenesis

Vidisha Mohad; Vlasta Lungova; Jamie Verheyden; Susan L Thibeault

doi:10.1016/j.ydbio.2021.01.012

Inactivation of Lats1 and Lats2 highlights the role of hippo pathway effector YAP in larynx and vocal fold epithelium morphogenesis

Dev Biol. 2021 May:473:33-49. doi: 10.1016/j.ydbio.2021.01.012. Epub 2021 Jan 28.

Authors

Vidisha Mohad¹, Vlasta Lungova², Jamie Verheyden³, Susan L Thibeault⁴

Affiliations

¹ Department of Surgery, University of Wisconsin-Madison, 5118 WIMR, 1111 Highland Avenue, Madison, WI, 53705, USA. Electronic address: mohad@surgery.wisc.edu.
² Department of Surgery, University of Wisconsin-Madison, 5118 WIMR, 1111 Highland Avenue, Madison, WI, 53705, USA. Electronic address: lungova@surgery.wisc.edu.
³ Department of Pediatrics, University of California San Diego, 9500 Gilman Drive, CMME Rm 1087D La Jolla, CA, 92093, USA. Electronic address: jverheyden@health.ucsd.edu.
⁴ Department of Surgery, University of Wisconsin School of Medicine and Public Health, 5103 WIMR, 1111 Highland Avenue, Madison, WI, 53705, USA. Electronic address: thibeault@surgery.wisc.edu.

Abstract

Proliferation and differentiation of vocal fold epithelial cells during embryonic development is poorly understood. We examined the role of Hippo signaling, a vital pathway known for regulating organ size, in murine laryngeal development. Conditional inactivation of the Hippo kinase genes Lats1 and Lats2, specifically in vocal fold epithelial cells, resulted in severe morphogenetic defects. Deletion of Lats1 and Lats2 caused abnormalities in epithelial differentiation, epithelial lamina separation, cellular adhesion, basement membrane organization with secondary failed cartilage, and laryngeal muscle development. Further, Lats1 and Lats2 inactivation led to failure in differentiation of p63+ basal progenitors. Our results reveal novel roles of Hippo-Lats-YAP signaling in proper regulation of VF epithelial fate and larynx morphogenesis.

Keywords: Epithelial progenitors; Hippo; Larynx; Lat 1; Lats2; YAP.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism*
Adaptor Proteins, Signal Transducing / physiology
Animals
Cell Cycle Proteins / metabolism
Cell Differentiation
Cell Proliferation / physiology
Epithelial Cells / metabolism
Epithelium / physiology
Female
Hippo Signaling Pathway
Larynx / metabolism
Larynx / physiology*
Male
Mice
Mice, Inbred C57BL
Morphogenesis
Protein Serine-Threonine Kinases / metabolism*
Protein Serine-Threonine Kinases / physiology
Signal Transduction / physiology
Transcription Factors / metabolism
Tumor Suppressor Proteins / metabolism*
Tumor Suppressor Proteins / physiology
Vocal Cords / metabolism
Vocal Cords / physiology
YAP-Signaling Proteins

Substances

Adaptor Proteins, Signal Transducing
Cell Cycle Proteins
Transcription Factors
Tumor Suppressor Proteins
YAP-Signaling Proteins
Yap1 protein, mouse
Lats1 protein, mouse
LATS2 protein, mouse
Protein Serine-Threonine Kinases

Abstract

Publication types

MeSH terms

Substances

Grants and funding