Stage-dependent craniofacial defects resulting from Sprouty2 overexpression

Dev Dyn. 2007 Jul;236(7):1918-28. doi: 10.1002/dvdy.21195.

Abstract

Sprouty genes encode intracellular regulators of receptor tyrosine kinases that function in a variety of developmental events. Although mice carrying null mutations in Sprouty genes exhibit craniofacial anomalies, the precise role of these regulatory proteins in facial development remains unclear. Here, we show that overexpression of spry2 at the initiation of craniofacial development results in a dramatic arrest in outgrowth of the facial prominences. Although endogenous spry2 and fibroblast growth factor 8 (fgf8) are coexpressed throughout much of craniofacial development, overexpression of spry2 did not alter the spatiotemporal patterns of fgf target gene expression. The morphological consequences of spry2 overexpression were specific: all of the facial prominences were truncated, but despite this gross malformation, the programs of osteogenesis and chondrogenesis were not impaired. Collectively, these data suggest that Sprouty2 plays a role in the outgrowth of facial prominences independent of canonical Fgf signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chick Embryo
  • Cleft Lip / genetics
  • Cleft Lip / metabolism
  • Cleft Palate / genetics
  • Cleft Palate / metabolism
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / metabolism*
  • Fibroblast Growth Factor 8 / biosynthesis
  • Fibroblast Growth Factor 8 / genetics
  • Fibroblast Growth Factors / physiology
  • Gene Expression Regulation, Developmental*
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics*
  • Signal Transduction / genetics

Substances

  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors