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Osr1 functions downstream of Hedgehog pathway to regulate foregut development
Lu Han1, Jingyue Xu1, Emily Grigg1
1Division of Developmental Biology, Center for Stem Cell & Organoid Medicine, Perinatal Institute, Cincinnati Children's Hospital, College of Medicine, University of Cincinnati, Cincinnati OH 45229, USA.
Developmental Biology
|May 15, 2017
Summary
The zinc finger transcription factor Osr1 is a novel downstream target of Hedgehog (HH) signaling. Osr1 is crucial for lung development, including progenitor formation, branching, and mesenchymal differentiation in the foregut.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Hedgehog (HH) signaling is vital for fetal development, coordinating respiratory, digestive, and cardiovascular systems.
- Disruptions in HH signaling can cause congenital defects, but downstream mechanisms remain unclear.
Purpose of the Study:
- To identify novel downstream targets of HH signaling in foregut development.
- To elucidate the role of Osr1 in respiratory system formation.
Main Methods:
- Analysis of Osr1 expression in relation to HH signaling.
- ChIP-seq to identify Gli3 binding sites near Osr1.
- Generation and analysis of Osr1 germline mutants.
- Tissue-specific conditional knockouts and lineage tracing in mice.
Main Results:
- Osr1 expression is dependent on HH signaling, with Gli3 binding near the Osr1 promoter.
- Osr1 mutants show reduced lung progenitors, abnormal lung lobe positioning, and impaired mesenchymal differentiation (pulmonary arteries, smooth muscle, cartilage).
- Osr1 acts cell-autonomously in the foregut mesenchyme.
Conclusions:
- Osr1 is a novel downstream target of the HH pathway.
- Osr1 is essential for lung specification, branching morphogenesis, and differentiation of foregut mesenchyme.
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