Retinoic acid selectively regulates Fgf10 expression and maintains cell identity in the prospective lung field of the developing foregut

Autor: George R. Flentke, Tushar J. Desai, Wellington V. Cardoso, Susan M. Smith, Sarah Malpel
Rok vydání: 2004
Předmět:
Thyroid Nuclear Factor 1
Mouse
Receptors
Retinoic Acid
Organogenesis
Fibroblast growth factor
Thyroid Gland
Retinoic acid
Ttf1
Rats
Sprague-Dawley
Mice
chemistry.chemical_compound
0302 clinical medicine
Lung
In Situ Hybridization
Regulation of gene expression
0303 health sciences
Vitamin A Deficiency
Endoderm
Foregut development
Gene Expression Regulation
Developmental
Nuclear Proteins
Cell biology
medicine.anatomical_structure
embryonic structures
Lung development
Lung morphogenesis
Signal Transduction
medicine.medical_specialty
Mesoderm
Mice
Transgenic
Tretinoin
Biology
03 medical and health sciences
Internal medicine
medicine
Animals
RNA
Messenger
Pancreas
Molecular Biology
030304 developmental biology
FGF10
Fgf10
Foregut
Cell Biology
Rats
Fibroblast Growth Factors
Endocrinology
chemistry
Digestive System
Fibroblast Growth Factor 10
030217 neurology & neurosurgery
Transcription Factors
Developmental Biology
Zdroj: Developmental Biology. 273:402-415
ISSN: 0012-1606
DOI: 10.1016/j.ydbio.2004.04.039
Popis: Although respiratory tract defects that result from disruption of retinoic acid (RA) signaling have been widely reported, the mechanism by which endogenous RA regulates early lung morphogenesis is unknown. Here, we provide novel evidence that a major role for RA is to selectively maintain mesodermal proliferation and induce fibroblast growth factor 10 (Fgf10) expression in the foregut region where the lung forms. By using a pan-RAR antagonist (BMS493) in foregut explant cultures, we show that bud initiation is selectively blocked in the prospective respiratory region by failure to induce Fgf10 in the corresponding mesoderm. The RA regulation of Fgf10 expression occurs only in this region, within a defined developmental window, and is not seen in other foregut derivatives such as thyroid and pancreas where Fgf10 is also required for normal development. Furthermore, we show that RA activity is essential in the lung field to maintain lung cell identity in the endoderm; RAR antagonism disrupts expression of thyroid transcription factor 1 (Ttf1), an early marker of the respiratory region in the endoderm, and surfactant protein C (Sp-C) mRNAs. Our observations in mouse foregut cultures are corroborated by data from an in vivo model of vitamin A deficiency in rats. Our study supports RA as an essential regulator of gene expression and cellular activities during primary bud formation.
Databáze: OpenAIRE
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