# Role of the Hippo-Yap signaling pathway in organ of Corti

> **NIH NIH R21** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $165,000

## Abstract

Project Summary/Abstract:
 The intricate tissue architecture established during organ of Corti development requires precise
temporal coordination between arrest of cell proliferation and initiation of sensory cell differentiation. Despite
the necessity for this complex patterning, the mechanism regulating cell-cycle exit in the developing organ of
Corti remains poorly understood.
 This proposal is aimed at investigating the role of Hippo signaling—a pathway that has recently
emerged as an important regulator of growth control—in organ of Corti morphogenesis. Unlike most signaling
cascades, Hippo is repressive in nature, and it is activated mechanically through increased cell density, cell-
cell contacts, and tissue stiffness. The main experimental objective of the current proposal is to investigate
whether genetic manipulation of the transcription co-factor Yap—a downstream target of Hippo—regulates cell
proliferation and cell-cycle exit in the developing inner ear. To interrogate this premise, Cre-loxP mediated
gene knockout will be implemented for loss of function experiments (Aim 1), and viral expression of a
constitutively active form of Yap will be used to assess gain-of-function conditions (Aim 3). Additionally, a novel
three-dimensional cochlear organ culture will be used to study the role of mechanical force of Yap protein
degradation and cell-cycle exit in the developing organ of Corti.
 The proposed basic research has a long-term therapeutic potential. Understanding the role of Yap in
triggering the arrest of prosensory-cell proliferation during early stages of organ of Corti development is critical
in efforts to characterize the molecular signaling network governing its morphogenesis. A more complete
understanding of organ of Corti development will aid in relieving the restriction on proliferative response in the
surviving populations of inner ear supporting cells, which is the major impediment to hair-cell regeneration in
mammals.

## Key facts

- **NIH application ID:** 9951018
- **Project number:** 5R21DC016984-03
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Ksenia Gnedeva
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $165,000
- **Award type:** 5
- **Project period:** 2018-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9951018

## Citation

> US National Institutes of Health, RePORTER application 9951018, Role of the Hippo-Yap signaling pathway in organ of Corti (5R21DC016984-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9951018. Licensed CC0.

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