Tbx1, a DiGeorge syndrome candidate gene, is regulated by sonic hedgehog during pharyngeal arch development

Dev Biol. 2001 Jul 1;235(1):62-73. doi: 10.1006/dbio.2001.0283.


Appropriate interactions between the epithelium and adjacent neural crest-derived mesenchyme are necessary for normal pharyngeal arch development. Disruption of pharyngeal arch development in humans underlies many of the craniofacial defects observed in the 22q11.2 deletion syndrome (del22q11), but the genes responsible remain unknown. Tbx1 is a T-box transcription factor that lies in the 22q11.2 locus. Tbx1 transcripts were found to be localized to the pharyngeal endoderm and the mesodermal core of the pharyngeal arches, but were not present in the neural crest-derived mesenchyme of the pharyngeal arches. Sonic hedgehog (Shh) is also expressed in the pharyngeal arches and is necessary for normal craniofacial development. We found that Tbx1 expression was dependent upon Shh signaling in mouse embryos, consistent with their overlapping expression in the pharyngeal arches. Furthermore, Shh was sufficient to induce Tbx1 expression when misexpressed in selected regions of chick embryos. These studies reveal a Shh-mediated pathway that regulates Tbx1 during pharyngeal arch development.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chick Embryo
  • Chromosome Deletion
  • Chromosomes, Human, Pair 22
  • Cloning, Molecular
  • DNA Primers
  • DNA, Complementary
  • DiGeorge Syndrome / genetics*
  • Gene Expression Regulation, Developmental / physiology*
  • Hedgehog Proteins
  • Humans
  • In Situ Hybridization
  • Mice
  • Molecular Sequence Data
  • Pharynx / embryology*
  • Proteins / physiology*
  • RNA, Messenger / genetics
  • Sequence Homology, Amino Acid
  • T-Box Domain Proteins / chemistry
  • T-Box Domain Proteins / genetics*
  • Trans-Activators*


  • DNA Primers
  • DNA, Complementary
  • Hedgehog Proteins
  • Proteins
  • RNA, Messenger
  • SHH protein, human
  • T-Box Domain Proteins
  • TBX1 protein, human
  • Tbx1 protein, mouse
  • Trans-Activators