P2.36. AMOTL2 IN THE BRAIN: FROM DEVELOPMENT TO POSTNATAL
Ila Joshi1,2, Anthony Kischel1, Przemysław Kaczor1, Katarzyna O. Rojek3, Tomasz J. Prószyński1
1 Laboratory of Synaptogenesis, Łukasiewicz Research Network – PORT Polish Center for Technology Development, Stabłowicka 147, 54-066 Wrocław, Poland
2 Ludwik Hirszfeld Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland
3 Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
INTRODUCTION: Angiomotins, which include AMOT, AMOTL1, and AMOTL2, are scaffolding proteins mainly studied for their role in regulating the Hippo signaling pathway and cancer. However, the function of Angiomotins in the CNS is widely unknown; AMOT has been reported to regulate dendritic outgrowth and spine formation. However, AMOTL2 functions within the brain remain unexplored.
AIM(S): We aim to elucidate the role of AMOTL2 in neural progenitors and its function in differentiated neurons.
METHOD(S): We generated a conditional knockout (cKO) mouse model using the Nestin-Cre line, enabling early deletion of AMOTL2 in neural progenitors. Histological and molecular analyses were performed on neonatal brains to assess changes in brain morphology and cell populations. In addition, cellular and molecular assays were conducted to explore AMOTL2 function in mature neurons.
RESULTS: Our In situ hybridization (ISH) results indicate that AMOTL2 is expressed in both neural progenitors and differentiated neurons, suggesting that it may serve distinct functions at different stages of neurodevelopment. To investigate its role, we generated a conditional knockout using the Nestin-Cre mouse line, targeting AMOTL2 deletion in neural progenitors that give rise to both neurons and astrocytes. This early deletion resulted in altered brain morphology in newborn mice, along with changes in neural progenitors and differentiated neuronal populations.
In parallel, our advanced molecular and cellular studies demonstrated that AMOTL2 may also play important functions in differentiated neurons that can affect brain functioning within specific brain regions and subcircuits
CONCLUSIONS: Collectively, our results point to important AMOTL2 functions in the central nervous system. We are currently employing a combination of molecular, cellular, and behavioral approaches to further elucidate the role of AMOTL2 in the brain.
FINANCIAL SUPPORT: This research was supported by Polish National Science Center grants Opus 2022/45/B/NZ3/03688 and Preludium 2024/53/N/NZ3/03243.