beta-Catenin promotes respiratory progenitor identity in mouse foregut.
The mammalian respiratory system, consisting of both trachea and lung, initiates from the foregut endoderm. The molecular program that instructs endodermal cells to adopt the respiratory fate is not fully understood. Here we show that conditional inactivation of beta-Catenin (also termed Ctnnb1) in foregut endoderm leads to absence of both the trachea and lung due to a failure in maintaining the respiratory fate. In converse, conditional expression of an activated form of beta-Catenin leads to expansion of Nkx2.1, an early marker for the trachea and lung, into adjacent endoderm including the stomach epithelium. Analyses of these mutants show that the loss or gain of trachea/lung progenitor identity is accompanied by an expansion or contraction of esophagus/stomach progenitor identity, respectively. Our findings reveal an early role for beta-Catenin in the establishment of respiratory progenitors in mouse foregut endoderm.
Harris-Johnson
Kelley S
KS
Laboratory of Genetics and Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
Domyan
Eric T
ET
Vezina
Chad M
CM
Sun
Xin
X
D000818:Animals; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000378:metabolism; D004707:Endoderm / Q000002:abnormalities / Q000378:metabolism; D005260:Female; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008168:Lung / Q000002:abnormalities* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012137:Respiratory System / Q000196:embryology* / Q000378:metabolism; D015619:Respiratory System Abnormalities / Q000235:genetics / Q000503:physiopathology; D015398:Signal Transduction; D014132:Trachea / Q000002:abnormalities* / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D051153:Wnt Proteins; D051176:beta Catenin