Related Experiment Video
Updated: Mar 27, 2026
3D Modeling of the Lateral Ventricles and Histological Characterization of Periventricular Tissue in Humans and Mouse
Published on: May 19, 2015
Yap is required for ependymal integrity and is suppressed in LPA-induced hydrocephalus
Raehee Park1,2, Uk Yeol Moon1,2, Jun Young Park1,2
1Shriners Hospitals Pediatrics Research Center, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Insights
The Hippo pathway
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Ependymal cell development is crucial for preventing fetal hydrocephalus.
- The Hippo pathway and its effector Yap are involved in tissue development.
Purpose of the Study:
- To investigate the role of Yap in ependymal cell development and hydrocephalus.
- To understand how lysophosphatidic acid (LPA) affects Yap and ependymal cells.
Main Methods:
- Studied Yap's role in progenitor proliferation and cell attachment.
- Investigated LPA's effect on Yap and N-cadherin in the developing aqueduct.
- Utilized forced Yap expression and phosphomimetic Yap for restoration experiments.
Main Results:
- Yap is essential for generating ependymal cells and proper development.
- LPA exposure deregulates Yap and causes loss of N-cadherin in the aqueduct.
- Forced Yap expression partially restores N-cadherin, improving tissue junctions.
Conclusions:
- Yap is a key regulator of ependymal cell development and tissue integrity.
- Yap plays a novel role in maintaining tissue junctions during development and injury.
- Targeting Yap may offer therapeutic strategies for fetal hydrocephalus.
Abstract:
Timely generation and normal maturation of ependymal cells along the aqueduct are critical for preventing physical blockage between the third and fourth ventricles and the development of fetal non-communicating hydrocephalus. Our study identifies Yap, the downstream effector of the evolutionarily conserved Hippo pathway, as a central regulator for generating developmentally controlled ependymal cells along the ventricular lining of the aqueduct. Yap function is necessary for proper proliferation of progenitors and apical attachment of ependymal precursor cells. Importantly, an injury signal initiated by lysophosphatidic acid (LPA), an upstream regulator of Yap that can cause fetal haemorrhagic hydrocephalus, deregulates Yap in the developing aqueduct. LPA exposure leads to the loss of N-cadherin concentrations at the apical endfeet, which can be partially restored by forced Yap expression and more efficiently by phosphomimetic Yap. These results reveal a novel function of Yap in retaining tissue junctions during normal development and after fetal brain injury.
