Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/48475

TitleRetinoic acid regulates avian lung branching through a molecular network
Author(s)Silva, Hugo Fernandes
Cunha, Patrícia Vaz
Barbosa, Violina Baranauskaite
Gonçalves, Carla Silva
Pinto, Jorge Correia
Moura, Rute S.
KeywordsChick lung
Pulmonary development
Branching morphogenesis
Signaling pathways
sox2
sox9
Issue dateAug-2017
PublisherSpringer
JournalCellular and Molecular Life Sciences
Abstract(s)Retinoic acid (RA) is of major importance during vertebrate embryonic development and its levels need to be strictly regulated otherwise congenital malformations will develop. Through the action of specific nuclear receptors, named RAR/RXR, RA regulates the expression of genes that eventually influence proliferation and tissue patterning. RA has been described as crucial for different stages of mammalian lung morphogenesis, and as part of a complex molecular network that contributes to precise organogenesis; nonetheless, nothing is known about its role in avian lung development. The current report characterizes, for the first time, the expression pattern of RA signaling members (stra6, raldh2, raldh3, cyp26a1, rar alpha, and rar beta) and potential RA downstream targets (sox2, sox9, meis1, meis2, tgf beta 2, and id2) by in situ hybridization. In the attempt of unveiling the role of RA in chick lung branching, in vitro lung explants were performed. Supplementation studies revealed that RA stimulates lung branching in a dose-dependent manner. Moreover, the expression levels of cyp26a1, sox2, sox9, rar beta, meis2, hoxb5, tgf beta 2, id2, fgf10, fgfr2, and shh were evaluated after RA treatment to disclose a putative molecular network underlying RA effect. In situ hybridization analysis showed that RA is able to alter cyp26a1, sox9, tgf beta 2, and id2 spatial distribution; to increase rar beta, meis2, and hoxb5 expression levels; and has a very modest effect on sox2, fgf10, fgfr2, and shh expression levels. Overall, these findings support a role for RA in the proximal-distal patterning and branching morphogenesis of the avian lung and reveal intricate molecular interactions that ultimately orchestrate branching morphogenesis.
TypeArticle
URIhttp://hdl.handle.net/1822/48475
DOI10.1007/s00018-017-2600-3
ISSN1420-682X
1420-9071
Publisher versionhttps://link.springer.com/article/10.1007%2Fs00018-017-2600-3
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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