Unraveling PRR12 mechanisms in neuroocular syndrome: a multi-model approach and therapeutic perspectives

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2025.

Our research focuses on PRR12, a gene whose inactivation causes a syndrome that affects brain and eye development, yet its role remains unclear. Because the alterations responsible for the syndrome occur during the embryonic phase, it is not possible to study the molecular mechanisms directly in humans. For this reason, we have developed several experimental models in our laboratory that reproduce PRR12 inactivation. We use human cell models derived from induced pluripotent stem cells, as well as mouse and zebrafish models, to understand how PRR12 influences brain development and function. In our cell models, we have observed that disabling PRR12 leads to excessive proliferation of neural precursor cells and impairs their maturation; we will analyze these effects through tests that examine cell behavior, structure, and activity, including organoids that assess neural connections. In the mouse and zebrafish models, which exhibit defects similar to those observed in patients—such as growth delays, abnormalities in the brain, eyes, and heart, and repetitive behaviors—we will perform molecular, cellular, and behavioral analyses to evaluate the consequences of PRR12 inactivation in whole organisms. Finally, we will explore strategies to mitigate or counteract the effects of the PRR12 mutation. By integrating the information obtained from these models, our study aims to unveil the mechanisms underlying PRR12-related disorders and to identify potential therapeutic treatments.