2026-08-29T14:07:44Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/264042025-12-18T12:56:49Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587

00925njm 22002777a 4500 dc Chávez, Myra N author Arora, Prateek author Meer, Marco author Marques, Ines J author Ernst, Alexander author Morales Castro, Rodrigo A author Mercader, Nadia author 2024-12-20 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. iScience. 2024 Nov 19;27(12):111406. iScience 39720516 https://hdl.handle.net/20.500.12105/26404 Cell biology Developmental biology Model organism Molecular biology Transcriptomics Spns1-dependent endocardial lysosomal function drives valve morphogenesis through Notch1-signaling.