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Non-redundant role for the transcription factor Gli1 at multiple stages of thymocyte development

  • Anna Furmanski
    ,
  • Ekati Drakopoulou
    ,
  • Susan V. Outram
    ,
  • Nicola J. Rowbotham
    ,
  • Susan Ross
    ,
  • Jose Ignacio Saldana
  • University College London
Research Output: Contribution to journal Article Peer-review

Abstract

The Hedgehog (Hh) signaling pathway influences multiple stages of murine T-cell development. Hh signaling mediates transcriptional changes by the activity of the Gli family of transcription factors, Gli1, Gli2 and Gli3. Both Gli2 and Gli3 are essential for mouse developmentand can be processed to function as transcriptional repressors or transcriptional activators, whereas Gli1, itself a transcriptional target of Hh pathway activation, can only function as a transcriptional activator and is not essential for mouse development. Gli1-deficient mice are healthy and appear normal and nonredundant functions for Gli1 have been difficult to identify. Here we show that Gli1 is non-redundant in the regulation of T-cell development in the thymus, at multiple developmental stages. Analysis of Gli1-deficient embryonic mouse thymus shows a role for Gli1 to promote the differentiation of CD4⁻CD8⁻ double negative (DN) thymocytes before pre- TCR signal transduction, and a negative regulatory function after pre-TCR signaling. In addition, introduction of a Class I-restricted transgenic TCR into the adult Gli1-deficient and embryonic Gli2-deficient thymus showed that both Gli1 and Gli2 influence its selection to the CD8 lineage.

Publication Information

Output type

Research Output: Contribution to journal Article Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 4144-4152

Journal (Volume, Issue Number)

Cell Cycle (Volume 9, Issue 20)

Publication milestones

  • Published - 15/10/2010

Publication status

Published - 15/10/2010

ISSN

1538-4101

External Publication IDs

  • handle.net: 10547/623407
  • Scopus: 77958470617

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