Chávez, Myra NArora, PrateekMeer, MarcoMarques, Ines JErnst, AlexanderMorales Castro, Rodrigo AMercader, Nadia2025-03-102025-03-102024-12-20iScience. 2024 Nov 19;27(12):111406.https://hdl.handle.net/20.500.12105/26404This work was supported by grants 310030L_182575 from the Swiss National Science Foundation and H2020-SC1-2019-Single-Stage-RTD REANIMA-874764 to N.M., SELF2020-23 from University of Bern, Swiss Life research grant 2021 and ESC Basic Research Fellowship 2022 to M.N.C.Autophagy-lysosomal degradation is a conserved homeostatic process considered to be crucial for cardiac morphogenesis. However, both its cell specificity and functional role during heart development remain unclear. Here, we introduced zebrafish models to visualize autophagic vesicles and track their temporal and cellular localization in the larval heart. We observed a significant accumulation of autolysosomal and lysosomal vesicles in the atrioventricular and bulboventricular regions and their respective valves. We addressed the role of lysosomal degradation based on the Spinster homolog 1 () mutant (, ). larvae displayed morphological and functional cardiac defects, including abnormal endocardial organization, impaired valve formation and retrograde blood flow. Single-nuclear transcriptome analyses revealed endocardial-specific differences in lysosome-related genes and alterations of signalling. Endocardial-specific overexpression of and rescued features of valve formation and function. Altogether, our results reveal a cell-autonomous role of lysosomal processing during cardiac valve formation affecting signalling.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/Cell biologyDevelopmental biologyModel organismMolecular biologyTranscriptomicsAttribution-NonCommercial-NoDerivatives 4.0 International3972051627(12)111406iScienceopen access