2026-08-29T14:07:35Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/264042025-12-18T12:56:49Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587
Repisalud
author
Chávez, Myra N
author
Arora, Prateek
author
Meer, Marco
author
Marques, Ines J
author
Ernst, Alexander
author
Morales Castro, Rodrigo A
author
Mercader, Nadia
funder
Swiss National Science Foundation
funder
Unión Europea. Comisión Europea. H2020
2025-03-10T14:39:03Z
2025-03-10T14:39:03Z
2024-12-20
iScience. 2024 Nov 19;27(12):111406.
iScience
39720516
https://hdl.handle.net/20.500.12105/26404
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.
eng
Cell biology
Developmental biology
Model organism
Molecular biology
Transcriptomics
Spns1-dependent endocardial lysosomal function drives valve morphogenesis through Notch1-signaling.
research article
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URL
https://repisalud.isciii.es/bitstreams/bd46f30d-83af-4976-a0be-e4f2ed9f2c63/download
File
MD5
e328afbf7266fc40d70186f67309ac0a
13608011
application/pdf
Spns1-dependent endocardial_iScience_2024.pdf