Browsing by Author "Fonseca, Catarina G."
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- Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changesPublication . Fidalgo, Marta F.; Fonseca, Catarina G.; Caldas, Paulo; Raposo, Alexandre A. S. F.; Balboni, Tania; Henao-Mišíková, Lenka; Grosso, Ana R.; Vasconcelos, Francisca F.; Franco, Cláudio A.Adaptation to breathing is a critical step in lung function and it is crucial for organismal survival. Alveoli are the lung gas exchange units and their development, from late embryonic to early postnatal stages, requires feedbacks between multiple cell types. However, how the crosstalk between the alveolar cell types is modulated to anticipate lung adaptation to breathing is still unclear. Here, we uncovered a synchronous alternative splicing switch in multiple genes in the developing mouse lungs at the transition to birth, and we identified hnRNP A1, Cpeb4, and Elavl2/HuB as putative splicing regulators of this transition. Notably, we found that Vegfa switches from the Vegfa 164 isoform to the longer Vegfa 188 isoform exclusively in lung alveolar epithelial AT1 cells. Functional analysis revealed that VEGFA 188 (and not VEGFA 164) drives the specification of Car4-positive aerocytes, a subtype of alveolar endothelial cells specialized in gas exchanges. Our results reveal that the cell type-specific regulation of Vegfa alternative splicing just before birth modulates the epithelial-endothelial crosstalk in the developing alveoli to promote lung adaptation to breathing.
- Competition for endothelial cell polarity drives vascular morphogenesis in the mouse retinaPublication . Barbacena, Pedro; Dominguez-Cejudo, Maria; Fonseca, Catarina G.; Gómez-González, Manuel; Faure, Laura M.; Zarkada, Georgia; Pena, Andreia; Pezzarossa, Anna; Ramalho, Daniela; Giarratano, Ylenia; Ouarné, Marie; Barata, David; Fortunato, Isabela C.; Misikova, Lenka Henao; Mauldin, Ian; Carvalho, Yulia; Trepat, Xavier; Roca-Cusachs, Pere; Eichmann, Anne; Bernabeu, Miguel O.; Franco, Cláudio A.Blood-vessel formation generates unique vascular patterns in each individual. The principles governing the apparent stochasticity of this process remain to be elucidated. Using mathematical methods, we find that the transition between two fundamental vascular morphogenetic programs—sprouting angiogenesis and vascular remodeling—is established by a shift of collective front-to-rear polarity of endothelial cells in the mouse retina. We demonstrate that the competition between biochemical (VEGFA) and mechanical (blood-flow-induced shear stress) cues controls this collective polarity shift. Shear stress increases tension at focal adhesions overriding VEGFA-driven collective polarization, which relies on tension at adherens junctions. We propose that vascular morphogenetic cues compete to regulate individual cell polarity and migration through tension shifts that translates into tissue-level emergent behaviors, ultimately leading to uniquely organized vascular patterns.