Mesenchymal fibroblast growth factor receptor signaling regulates palatal shelf elevation during secondary palate formation

Kai Yu, Kannan Karuppaiah, David M. Ornitz

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Background: Palatal shelf elevation is an essential morphogenetic process during secondary palate closure and failure or delay of palatal shelf elevation is a common cause of cleft palate, one of the most common birth defects in humans. Here, we studied the role of mesenchymal fibroblast growth factor receptor (FGFR) signaling during palate development by conditional inactivation of Fgfrs using a mesenchyme-specific Dermo1-Cre driver. Results: We showed that Fgfr1 is expressed throughout the palatal mesenchyme and Fgfr2 is expressed in the medial aspect of the posterior palatal mesenchyme overlapping with Fgfr1. Mesenchyme-specific disruption of Fgfr1 and Fgfr2 affected palatal shelf elevation and resulted in cleft palate. We further showed that both Fgfr1 and Fgfr2 are expressed in mesenchymal tissues of the mandibular process but display distinct expression patterns. Loss of mesenchymal FGFR signaling reduced mandibular ossification and lower jaw growth resulting in abnormal tongue insertion in the oral-nasal cavity. Conclusions: We propose a model to explain how redundant Fgfr1 and Fgfr2 expression in the palatal and mandibular mesenchyme regulates shelf medial wall protrusion and growth of the mandible to coordinate the craniofacial tissue movements that are required for palatal shelf elevation.

Original languageEnglish
Pages (from-to)1427-1438
Number of pages12
JournalDevelopmental Dynamics
Volume244
Issue number11
DOIs
StatePublished - Nov 2015

Keywords

  • Cleft palate
  • Conditional gene knockout
  • FGFR gene expression
  • Mandible development
  • Palatal shelf elevation
  • Secondary palate development

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