Sonic hedgehog exerts distinct, stage-specific effects on tongue and taste papilla development

Dev Biol. 2004 Dec 15;276(2):280-300. doi: 10.1016/j.ydbio.2004.07.042.


Taste papillae are ectodermal specializations that serve to house and distribute the taste buds and their renewing cell populations in specific locations on the tongue. We previously showed that Sonic hedgehog (Shh) has a major role in regulating the number and spatial pattern of fungiform taste papillae on embryonic rat tongue, during a specific period of papilla formation from the prepapilla placode. Now we have immunolocalized the Shh protein and the Patched receptor protein (Ptc), and have tested potential roles for Shh in formation of the tongue, emergence of papilla placodes, development of papilla number and size, and maintenance of papillae after morphogenesis is advanced. Cultures of entire embryonic mandible or tongues from gestational days 12 to 18 [gestational or embryonic days (E)12-E18] were used, in which tongues and papillae develop with native spatial, temporal, and molecular characteristics. The Shh signaling pathway was disrupted with addition of cyclopamine, jervine, or the 5E1 blocking antibody. Shh and Ptc proteins are diffuse in prelingual tissue and early tongue swellings, and are progressively restricted to papilla placodes and then to regions of developing papillae. Ptc encircles the dense Shh immunoproduct in papillae at various stages. When the Shh signal is disrupted in cultures of E12 mandible, tongue formation is completely prevented. At later stages of tongue culture initiation, Shh signal disruption alters development of tongue shape (E13) and results in a repatterned fungiform papilla distribution that does not respect normally papilla-free tongue regions (E13-E14). Only a few hours of Shh signal disruption can irreversibly alter number and location of fungiform papillae on anterior tongue and elicit papilla formation on the intermolar eminence. However, once papillae are well formed (E16-E18), Shh apparently does not have a clear role in papilla maintenance, nor does the tongue retain competency to add fungiform papillae in atypical locations. Our data not only provide evidence for inductive and morphogenetic roles for Shh in tongue and fungiform papilla formation, but also suggest that Shh functions to maintain the interpapilla space and papilla-free lingual regions. We propose a model for Shh function at high concentration to form and maintain papillae and, at low concentration, to activate between-papilla genes that maintain a papilla-free epithelium.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Embryo, Mammalian
  • Female
  • Gestational Age
  • Hedgehog Proteins
  • Mandible / embryology
  • Mandible / metabolism
  • Membrane Proteins / metabolism
  • Microscopy, Electron, Scanning
  • Morphogenesis*
  • Patched Receptors
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface
  • Signal Transduction / drug effects
  • Taste Buds / embryology*
  • Taste Buds / metabolism
  • Tissue Culture Techniques
  • Tongue / anatomy & histology
  • Tongue / drug effects
  • Tongue / embryology*
  • Tongue / metabolism
  • Trans-Activators / metabolism*
  • Veratrum Alkaloids / pharmacology


  • Hedgehog Proteins
  • Membrane Proteins
  • Patched Receptors
  • Receptors, Cell Surface
  • Trans-Activators
  • Veratrum Alkaloids
  • jervine
  • cyclopamine