Transcription Factor 2I Regulates Neuronal Development via TRPC3 in 7q11.23 Disorder Models

Marielle H.S. Deurloo, Ekaterina Turlova, Wen Liang Chen, You Wei Lin, Elaine Tam, Nardos G. Tassew, Michael Wu, Ya Chi Huang, Jacqueline N. Crawley, Philippe P. Monnier, Alexander J.A. Groffen, Hong Shuo Sun*, Lucy R. Osborne, Zhong Ping Feng

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Williams syndrome (WS) and 7q11.23 duplication syndrome (Dup7q11.23) are neurodevelopmental disorders caused by the deletion and duplication, respectively, of ~ 25 protein-coding genes on chromosome 7q11.23. The general transcription factor 2I (GTF2I, protein TFII-I) is one of these proteins and has been implicated in the neurodevelopmental phenotypes of WS and Dup7q11.23. Here, we investigated the effect of copy number alterations in Gtf2i on neuronal maturation and intracellular calcium entry mechanisms known to be associated with this process. Mice with a single copy of Gtf2i (Gtf2i+/Del) had increased axonal outgrowth and increased TRPC3-mediated calcium entry upon carbachol stimulation. In contrast, mice with 3 copies of Gtf2i (Gtf2i+/Dup) had decreases in axon outgrowth and in TRPC3-mediated calcium entry. The underlying mechanism was that TFII-I did not affect TRPC3 protein expression, while it regulated TRPC3 membrane translocation. Together, our results provide novel functional insight into the cellular mechanisms that underlie neuronal maturation in the context of the 7q11.23 disorders.

Original languageEnglish
Pages (from-to)3313-3325
Number of pages13
JournalMolecular Neurobiology
Issue number5
Early online date17 Aug 2018
Publication statusPublished - May 2019


  • Animals
  • Axons/metabolism
  • Calcium/metabolism
  • Cell Membrane/metabolism
  • Chromosome Aberrations
  • Disease Models, Animal
  • Mice
  • Neurites/metabolism
  • Neurons/metabolism
  • Phenotype
  • TRPC Cation Channels/metabolism
  • Time Factors
  • Transcription Factors, TFII/metabolism
  • TRPC3
  • Williams-Beuren syndrome (WBS)
  • General transcription factor 2i
  • Cortical neurons


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