Open AccessFoxD1‐driven CCN2 deletion causes axial skeletal deformities, pulmonary hypoplasia, and neonatal asphyctic death
Author(s) -
Falke Lucas L.,
He Nannan,
Chuva de Sousa Lopes Susana M.,
Broekhuizen Roel,
Lyons Karen,
Nguyen Tri Q.,
Goldschmeding Roel
Publication year - 2019
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-020-00549-4
Subject(s) - ctgf , progenitor cell , pathology , medicine , mesenchymal stem cell , fibrosis , hypoplasia , lung , anatomy , growth factor , biology , stem cell , microbiology and biotechnology , receptor
Abstract Pulmonary fibrosis is a severely disabling disease often leading to death. CCN2 (Cellular Communication Network factor 2, also known as CTGF) is a known mediator of fibrosis and clinical trials studying anti‐CCN2 efficacy in pulmonary fibrosis are currently underway. Fork head box D1 (FoxD1) transcription factor is transiently expressed in several mesenchymal cell types, including those of fetal lungs. Differentiation of FoxD1‐progenitor derived pericytes into myofibroblasts involves CCN2 expression and contributes importantly to maladaptive tissue remodeling in e.g. kidney and lung fibrosis models. To generate a model for studying the contribution of CCN2 expression in FoxD1‐progenitor derived cells to development of fibrotic tissue remodeling, we set out to establish a FoxD1Cre ‐ CCN2 flox/flox mouse colony. However, all double‐transgenic mice died soon after birth due to asphyxia. Histopathological examination revealed a reduction in alveolar space and lung weight, and subtle axial (thoracic and cervical) skeletal deformities. Together with the previously reported association of a FoxD1 containing locus with human adolescent idiopathic scoliosis, our data suggest that the development of fatal pulmonary hypoplasia caused by selective deletion of CCN2 from FoxD1‐progenitor derived mesenchymal cells was secondary to aberrant axial skeletogenesis.