Frizzled 1 and frizzled 2 genes function in palate, ventricular septum and neural tube closure: general implications for tissue fusion processes

Development. 2010 Nov;137(21):3707-17. doi: 10.1242/dev.052001.


The closure of an open anatomical structure by the directed growth and fusion of two tissue masses is a recurrent theme in mammalian embryology, and this process plays an integral role in the development of the palate, ventricular septum, neural tube, urethra, diaphragm and eye. In mice, targeted mutations of the genes encoding frizzled 1 (Fz1) and frizzled 2 (Fz2) show that these highly homologous integral membrane receptors play an essential and partially redundant role in closure of the palate and ventricular septum, and in the correct positioning of the cardiac outflow tract. When combined with a mutant allele of the planar cell polarity gene Vangl2 (Vangl2(Lp)), Fz1 and/or Fz2 mutations also cause defects in neural tube closure and misorientation of inner ear sensory hair cells. These observations indicate that frizzled signaling is involved in diverse tissue closure processes, defects in which account for some of the most common congenital anomalies in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Fusion
  • Epistasis, Genetic / physiology
  • Female
  • Frizzled Receptors / genetics
  • Frizzled Receptors / metabolism
  • Frizzled Receptors / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Biological
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • Neural Tube / embryology*
  • Neural Tube / metabolism
  • Neural Tube / physiology
  • Palate / embryology*
  • Palate / metabolism
  • Pregnancy
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, G-Protein-Coupled / physiology*
  • Ventricular Septum / embryology*
  • Ventricular Septum / metabolism


  • Frizzled Receptors
  • Fzd1 protein, mouse
  • Fzd2 protein, mouse
  • Ltap protein, mouse
  • Nerve Tissue Proteins
  • Receptors, G-Protein-Coupled