Back to Search
Start Over
Mark1 regulates distal airspace expansion through type I pneumocyte flattening in lung development
- Source :
- Journal of cell science. 132(24)
- Publication Year :
- 2019
-
Abstract
- During the later stages of lung development, two types of pneumocytes, cuboidal type II (AECII) and flattened type I (AECI) alveolar epithelial cells, form distal lung saccules. Here, we highlight how fibroblasts expressing MAP-microtubule affinity regulating kinase 1 (Mark1) are required for the terminal stages of pulmonary development, called lung sacculation. In Mark1-knockout (KO) mice, distal sacculation and AECI flattening are significantly impaired. Fetal epithelial cells generate alveolar organoids and differentiate into pneumocytes when co-cultured with fibroblasts. However, the size of organoids decreased and AECI flattening was impaired in the presence of Mark1 KO fibroblasts. In Mark1 KO fibroblasts themselves, cilia formation and the Hedgehog pathway were suppressed, resulting in the loss of type I collagen expression. The addition of type I collagen restored AECI flattening in organoids co-cultured with Mark1 KO fibroblasts and rescued the decreased size of organoids. Mathematical modeling of distal lung sacculation supports the view that AECI flattening is necessary for the proper formation of saccule-like structures. These results suggest that Mark1-mediated fibroblast activation induces AECI flattening and thereby regulates distal lung sacculation.
- Subjects :
- Sacculation
Biology
Protein Serine-Threonine Kinases
Real-Time Polymerase Chain Reaction
Microtubules
03 medical and health sciences
Mice
0302 clinical medicine
Organoid
medicine
Animals
Fibroblast
Lung
Type-I Pneumocyte
030304 developmental biology
Mice, Knockout
0303 health sciences
Cilium
Epithelial Cells
Cell Biology
Fibroblasts
Models, Theoretical
Hedgehog signaling pathway
Coculture Techniques
Cell biology
medicine.anatomical_structure
Alveolar Epithelial Cells
030217 neurology & neurosurgery
Type I collagen
Subjects
Details
- ISSN :
- 14779137
- Volume :
- 132
- Issue :
- 24
- Database :
- OpenAIRE
- Journal :
- Journal of cell science
- Accession number :
- edsair.doi.dedup.....4be5c82edfa7fd0df693ee8bdcdf003f