Person: Loscertales, Maria
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Loscertales
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Maria
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Loscertales, Maria
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Publication Type IV collagen drives alveolar epithelial–endothelial association and the morphogenetic movements of septation(BioMed Central, 2016) Loscertales, Maria; Nicolaou, Fotini; Jeanne, Marion; Longoni, Mauro; Gould, Douglas B.; Sun, Yunwei; Maalouf, Faouzi I.; Nagy, Nandor; Donahoe, PatriciaBackground: Type IV collagen is the main component of the basement membrane that gives strength to the blood–gas barrier (BGB). In mammals, the formation of a mature BGB occurs primarily after birth during alveologenesis and requires the formation of septa from the walls of the saccule. In contrast, in avians, the formation of the BGB occurs rapidly and prior to hatching. Mutation in basement membrane components results in an abnormal alveolar phenotype; however, the specific role of type IV collagen in regulating alveologenesis remains unknown. Results: We have performed a microarray expression analysis in late chick lung development and found that COL4A1 and COL4A2 were among the most significantly upregulated genes during the formation of the avian BGB. Using mouse models, we discovered that mutations in murine Col4a1 and Col4a2 genes affected the balance between lung epithelial progenitors and differentiated cells. Mutations in Col4a1 derived from the vascular component were sufficient to cause defects in vascular development and the BGB. We also show that Col4a1 and Col4a2 mutants displayed disrupted myofibroblast proliferation, differentiation and migration. Lastly, we revealed that addition of type IV collagen protein induced myofibroblast proliferation and migration in monolayer culture and increased the formation of mesenchymal–epithelial septal-like structures in co-culture. Conclusions: Our study showed that type IV collagen and, therefore the basement membrane, play fundamental roles in coordinating alveolar morphogenesis. In addition to its role in the formation of epithelium and vasculature, type IV collagen appears to be key for alveolar myofibroblast development by inducing their proliferation, differentiation and migration throughout the developing septum. Electronic supplementary material The online version of this article (doi:10.1186/s12915-016-0281-2) contains supplementary material, which is available to authorized users.Publication MiR-449a Affects Epithelial Proliferation during the Pseudoglandular and Canalicular Phases of Avian and Mammal Lung Development(Public Library of Science, 2016) Sanford, Ethan L.; Choy, Kwong W.; Donahoe, Patricia; Tracy, Adam A.; Hila, Regis; Loscertales, Maria; Longoni, MauroCongenital diaphragmatic hernia is associated with pulmonary hypoplasia and respiratory distress, which result in high mortality and morbidity. Although several transgenic mouse models of lung hypoplasia exist, the role of miRNAs in this phenotype is incompletely characterized. In this study, we assessed microRNA expression levels during the pseudoglandular to canalicular phase transition of normal human fetal lung development. At this critical time, when the distal respiratory portion of the airways begins to form, microarray analysis showed that the most significantly differentially expressed miRNA was miR-449a. Prediction algorithms determined that N-myc is a target of miR-449a and identified the likely miR-449a:N-myc binding sites, confirmed by luciferase assays and targeted mutagenesis. Functional ex vivo knock-down in organ cultures of murine embryonic lungs, as well as in ovo overexpression in avian embryonic lungs, suggested a role for miR-449a in distal epithelial proliferation. Finally, miR-449a expression was found to be abnormal in rare pulmonary specimens of human fetuses with Congenital Diaphragmatic Hernia in the pseudoglandular or canalicular phase. This study confirms the conserved role of miR-449a for proper pulmonary organogenesis, supporting the delicate balance between expansion of progenitor cells and their terminal differentiation, and proposes the potential involvement of this miRNA in human pulmonary hypoplasia.Publication Erratum to: Type IV collagen drives alveolar epithelial–endothelial association and the morphogenetic movements of septation(BioMed Central, 2016) Loscertales, Maria; Nicolaou, Fotini; Jeanne, Marion; Longoni, Mauro; Gould, Douglas B.; Sun, Yunwei; Maalouf, Faouzi I.; Nagy, Nandor; Donahoe, Patricia