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Studying Wnt Signaling During Patterning of Conducting Airways
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Foxp2 and Foxp1 cooperatively regulate lung and esophagus development.

Weiguo Shu1, Min Min Lu, Yuzhen Zhang

  • 1Cardiovascular Institute, University of Pennsylvania, 956 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104, USA.

Development (Cambridge, England)
|April 13, 2007
PubMed
Summary

Transcription factors Foxp2 and Foxp1 are essential for lung and esophageal development. Their loss in mice causes severe defects in lung alveolarization and esophageal muscle formation, leading to lethality.

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Area of Science:

  • Developmental biology
  • Molecular genetics
  • Respiratory system physiology

Background:

  • Lung development involves complex branching morphogenesis.
  • Forkhead transcription factors Foxp2 and Foxp1 are expressed in foregut-derived tissues.
  • These factors play roles in tissue development and function.

Purpose of the Study:

  • Investigate the role of Foxp2 in postnatal lung development.
  • Determine if T1alpha is a target gene of Foxp2 and Foxp1.
  • Examine the combined effects of Foxp2 and Foxp1 loss on lung and esophageal development.

Main Methods:

  • Utilized mouse models with genetic alterations in Foxp2 and Foxp1.
  • Performed in vitro and in vivo assays to study gene regulation.
  • Analyzed lung alveolarization and esophageal muscle development morphologically.
  • Assessed the expression of key developmental regulators like N-myc and Hop.

Main Results:

  • Loss of Foxp2 in mice led to defective lung alveolarization and postnatal lethality.
  • T1alpha was identified as a direct target gene of both Foxp2 and Foxp1.
  • Combined loss of Foxp2 and partial loss of Foxp1 (Foxp2(-/-);Foxp1(+/-)) exacerbated lung defects and caused perinatal lethality.
  • Expression of N-myc and Hop was compromised in double mutant mice.
  • Esophageal muscle development was disrupted in Foxp2(-/-);Foxp1(+/-) embryos.

Conclusions:

  • Foxp2 and Foxp1 are critical regulators of lung and esophageal development.
  • These transcription factors are necessary for anterior foregut-derived tissue development.
  • Functional cooperation exists between Foxp1 and Foxp2 in co-expressed tissues.