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Distinct roles for retinoic acid receptors alpha and beta in early lung morphogenesis
- Source :
- Developmental Biology, Developmental Biology, Elsevier, 2006, 291 (1), pp.12-24. ⟨10.1016/j.ydbio.2005.10.045⟩
- Publisher :
- Elsevier Inc.
-
Abstract
- International audience; Retinoic acid (RA) signaling is required for normal development of multiple organs. However, little is known about how RA influences the initial stages of lung development. Here, we used a combination of genetic, pharmacological and explant culture approaches to address this issue, and to investigate how signaling by different RA receptors (RAR) mediates the RA effects. We analyzed initiation of lung development in retinaldehyde dehydrogenase-2 (Raldh2) null mice, a model in which RA signaling is absent from the foregut from its earliest developmental stages. We provide evidence that RA is dispensable for specification of lung cell fate in the endoderm. By using synthetic retinoids to selectively activate RAR alpha or beta signaling in this model, we demonstrate novel and unique functions of these receptors in the early lung. We show that activation of RAR beta, but not alpha, induces expression of the fibroblast growth factor Fgf10 and bud morphogenesis in the lung field. Similar analysis of wild type foregut shows that endogenous RAR alpha activity is required to maintain overall RA signaling, and to refine the RAR beta effects in the lung field. Our data support the idea that balanced activation of RAR alpha and beta is critical for proper lung bud initiation and endodermal differentiation.
- Subjects :
- MESH: Aldehyde Oxidoreductases
MESH: Signal Transduction
Receptors, Retinoic Acid
Organogenesis
Retinoic acid
Fibroblast growth factor
MESH: Mice, Knockout
Tissue Culture Techniques
Mice
chemistry.chemical_compound
0302 clinical medicine
Morphogenesis
MESH: Animals
Receptor
Lung
Mice, Knockout
0303 health sciences
SftpC
Retinoic Acid Receptor alpha
Endoderm
Foregut
Cell Differentiation
respiratory system
Aldehyde Oxidoreductases
Cell biology
MESH: Endoderm
Nkx2.1
embryonic structures
Lung development
Lung morphogenesis
Signal Transduction
MESH: Cell Differentiation
Alpha (ethology)
Biology
Cell fate determination
03 medical and health sciences
Raldh2
Animals
MESH: Lung
MESH: Tissue Culture Techniques
Molecular Biology
MESH: Mice
030304 developmental biology
MESH: Receptors, Retinoic Acid
FGF10
Fgf10
Endodermal specification
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology
Cell Biology
MESH: Morphogenesis
chemistry
Immunology
MESH: Fibroblast Growth Factor 10
Fibroblast Growth Factor 10
030217 neurology & neurosurgery
RAR
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 00121606 and 1095564X
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Developmental Biology
- Accession number :
- edsair.doi.dedup.....268fc53bc779e71d1695ce9387d3e468
- Full Text :
- https://doi.org/10.1016/j.ydbio.2005.10.045