PUBLICATION
Spns1-dependent endocardial lysosomal function drives valve morphogenesis through Notch1-signaling
- Authors
- Chávez, M.N., Arora, P., Meer, M., Marques, I.J., Ernst, A., Morales Castro, R.A., Mercader, N.
- ID
- ZDB-PUB-250109-34
- Date
- 2024
- Source
- iScience 27: 111406111406 (Journal)
- Registered Authors
- Marques, Ines, Mercader Huber, Nadia, Morales Castro, Rodrigo A.
- Keywords
- Cell biology, Developmental biology, Model organism, Molecular biology, Transcriptomics
- Datasets
- GEO:GSE246850
- MeSH Terms
- none
- PubMed
- 39720516 Full text @ iScience
Citation
Chávez, M.N., Arora, P., Meer, M., Marques, I.J., Ernst, A., Morales Castro, R.A., Mercader, N. (2024) Spns1-dependent endocardial lysosomal function drives valve morphogenesis through Notch1-signaling. iScience. 27:111406111406.
Abstract
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 in vivo 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 (spns1) mutant (not really started, nrs). nrs 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 notch1-signalling. Endocardial-specific overexpression of spns1 and notch1 rescued features of valve formation and function. Altogether, our results reveal a cell-autonomous role of lysosomal processing during cardiac valve formation affecting notch1-signalling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping