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Lung development requires an active ERK/MAPK pathway in the lung mesenchyme
Author(s) -
Boucherat Olivier,
LandryTruchon Kim,
Aoidi Rifdat,
Houde Nicolas,
Nadeau Valérie,
Charron Jean,
Jeannotte Lucie
Publication year - 2017
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.24464
Subject(s) - mesenchyme , mapk/erk pathway , biology , microbiology and biotechnology , wnt signaling pathway , mesenchymal stem cell , cancer research , signal transduction
Background: Reciprocal epithelial‐mesenchymal communications are critical throughout lung development, dictating branching morphogenesis and cell specification. Numerous signaling molecules are involved in these interactions, but the way epithelial‐mesenchymal crosstalk is coordinated remains unclear. The ERK/MAPK pathway transduces several important signals in lung formation. Epithelial inactivation of both Mek genes, encoding ERK/MAPK kinases, causes lung agenesis and death. Conversely, Mek mutation in mesenchyme results in lung hypoplasia, trachea cartilage malformations, kyphosis, omphalocele, and death. Considering the negative impact of kyphosis and omphalocele on intrathoracic space and, consequently, on lung growth, the exact role of ERK/MAPK pathway in lung mesenchyme remains unresolved. Results: To address the role of the ERK/MAPK pathway in lung mesenchyme in absence of kyphosis and omphalocele, we used the Tbx4 Cre deleter mouse line, which acts specifically in lung mesenchyme. These Mek mutants did not develop kyphosis and omphalocele but they presented lung hypoplasia, tracheal defects, and neonatal death. Tracheal cartilage anomalies suggested a role for the ERK/MAPK pathway in the control of chondrocyte hypertrophy. Moreover, expression data indicated potential interactions between the ERK/MAPK and canonical Wnt pathways during lung formation. Conclusions: Lung development necessitates a functional ERK/MAPK pathway in the lung mesenchymal layer in order to coordinate efficient epithelial‐mesenchymal interactions. Developmental Dynamics 246:72–82, 2017 . © 2016 Wiley Periodicals, Inc.