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A Shh-Foxf-Fgf18-Shh Molecular Circuit Regulating Palate Development
Jingyue Xu1, Han Liu1, Yu Lan1,2
1Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Plos Genetics
|January 9, 2016
Summary
Forkhead-box F2 (Foxf2) is crucial for normal palate development. This study reveals Foxf2 represses Fgf18, maintaining Shh expression for proper palatal shelf growth.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Cleft palate is a common birth defect.
- Sonic hedgehog (Shh) signaling is vital for palate development.
- Forkhead-box (Fox) transcription factors, including Foxf1 and Foxf2, are implicated in facial development.
Purpose of the Study:
- To elucidate the intrinsic role of Foxf2 in palate development.
- To understand the regulatory mechanisms by which Foxf2 controls palatogenesis.
Main Methods:
- Cre/loxP-mediated tissue-specific gene inactivation in mice.
- RNA-sequencing (RNA-seq) analysis of palatal mesenchyme.
- Whole mount in situ hybridization.
- Organotypic culture of palatal explants.
Main Results:
- Foxf2 is essential in neural crest-derived palatal mesenchyme for normal palatogenesis.
- Foxf2 deficiency leads to altered Shh signaling pathway gene expression (Shh, Ptch1, Shox2).
- Foxf2 represses Fgf18 expression in the palatal mesenchyme, which is critical for maintaining Shh expression in the palatal epithelium.
Conclusions:
- Foxf2 plays an intrinsic role in palate development.
- A novel Shh-Foxf-Fgf18-Shh regulatory circuit is identified in palate development.
- Foxf1 and Foxf2 regulate palatal shelf growth by modulating Fgf18 and Shh expression.
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