Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate.

• Classical research has suggested that early palate formation develops via epithelial-mesenchymal interactions, and in this study we reveal which signals control this process. Using Fgf10-/-, FGF receptor 2b-/- (Fgfr2b-/-), and Sonic hedgehog (Shh) mutant mice, which all exhibit cleft palate, we show that Shh is a downstream target of Fgf10/Fgfr2b signaling. Our results demonstrate that mesenchymal Fgf10 regulates the epithelial expression of Shh, which in turn signals back to the mesenchyme. This was confirmed by demonstrating that cell proliferation is decreased not only in the palatal epithelium but also in the mesenchyme of Fgfr2b-/- mice. These results reveal a new role for Fgf signaling in mammalian palate development. We show that coordinated epithelial-mesenchymal interactions are essential during the initial stages of palate development and require an Fgf-Shh signaling network.

Ämnesord

NATURVETENSKAP  -- Biologi -- Utvecklingsbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Developmental Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Odontologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dentistry (hsv//eng)

Nyckelord

Animals

Cell Division

physiology

Cleft Palate

etiology

metabolism

Culture Techniques

Epithelium

physiology

Fibroblast Growth Factor 10

Fibroblast Growth Factor 7

Fibroblast Growth Factors

genetics

metabolism

Hedgehog Proteins

In Situ Hybridization

In Situ Nick-End Labeling

Mesoderm

physiology

Mice

Mice

Knockout

Palate

cytology

embryology

Receptor

Fibroblast Growth Factor

Type 2

Receptors

Fibroblast Growth Factor

genetics

metabolism

Recombinant Fusion Proteins

genetics

metabolism

Signal Transduction

physiology

Trans-Activators

genetics

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)