BMP regulates regional gene expression in the dorsal otocyst through canonical and non-canonical intracellular pathways Academic Article uri icon


MeSH Major

  • Bone Morphogenetic Proteins
  • Ear, Inner
  • Gene Expression Regulation, Developmental
  • Signal Transduction


  • The inner ear consists of two otocyst-derived, structurally and functionally distinct components: the dorsal vestibular and ventral auditory compartments. BMP signaling is required to form the vestibular compartment, but how it complements other required signaling molecules and acts intracellularly is unknown. Using spatially and temporally controlled delivery of signaling pathway regulators to developing chick otocysts, we show that BMP signaling regulates the expression of Dlx5 and Hmx3, both of which encode transcription factors essential for vestibular formation. However, although BMP regulates Dlx5 through the canonical SMAD pathway, surprisingly, it regulates Hmx3 through a non-canonical pathway involving both an increase in cAMP-dependent protein kinase A activity and the GLI3R to GLI3A ratio. Thus, both canonical and non-canonical BMP signaling establish the precise spatiotemporal expression of Dlx5 and Hmx3 during dorsal vestibular development. The identification of the non-canonical pathway suggests an intersection point between BMP and SHH signaling, which is required for ventral auditory development.

publication date

  • June 15, 2016



  • Academic Article



  • eng

PubMed Central ID

  • PMC4920177

Digital Object Identifier (DOI)

  • 10.1242/dev.137133

PubMed ID

  • 27151948

Additional Document Info

start page

  • 2228

end page

  • 37


  • 143


  • 12