Non-redundant role for the transcription factor Gli1 at multiple stages of thymocyte development
Outram, Susan V.
Rowbotham, Nicola J.
Furmanski, Anna L.
Saldana, Jose Ignacio
Hager-Theodorides, Ariadne L.
MetadataShow full item record
AbstractThe 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.
CitationDrakopoulou E, Outram SV, Rowbotham NJ, Ross SE, Furmanski AL, Saldana JI, Hager-Theodorides AL, Crompton T (2010) 'Non-redundant role for the transcription factor Gli1 at multiple stages of thymocyte development', Cell Cycle, 9 (20), pp.4144-4152.
PublisherTaylor & Francis
PubMed Central IDPMC3055198
- Hedgehog signalling in T-cell development: a non-redundant role for Gli1.
- Authors: Bommhardt U
- Issue date: 2010 Nov 15
- Dissecting the functions of Gli transcription factors in T-cell development.
- Authors: Varas A, Sacedón R
- Issue date: 2010 Nov 15
- GLI3-dependent transcriptional repression of Gli1, Gli2 and kidney patterning genes disrupts renal morphogenesis.
- Authors: Hu MC, Mo R, Bhella S, Wilson CW, Chuang PT, Hui CC, Rosenblum ND
- Issue date: 2006 Feb
- Gli function is essential for motor neuron induction in zebrafish.
- Authors: Vanderlaan G, Tyurina OV, Karlstrom RO, Chandrasekhar A
- Issue date: 2005 Jun 15
- Mouse Gli1 mutants are viable but have defects in SHH signaling in combination with a Gli2 mutation.
- Authors: Park HL, Bai C, Platt KA, Matise MP, Beeghly A, Hui CC, Nakashima M, Joyner AL
- Issue date: 2000 Apr