Harris, Brett Stuart;
(2001)
Zinc-finger transcription factors in the Schwann cell lineage.
Doctoral thesis (Ph.D), UCL (University College London).
![]() |
Text
Zinc-finger_transcription_fact.pdf Download (17MB) |
Abstract
Myelin forming and non-myelin forming Schwann cells are the major glia within peripheral nerves. Recent studies have revealed the importance of the transcription factors Sox10, Pax3, Krox-20 and Oct-6 in Schwann cell development. This work describes one novel Schwann cell zinc-finger transcription factor, Zfp-57, and investigates the phenotype of Schwann cells deficient in another, Krox-24, with a view to discovering a function for these genes in Schwann cells. Zfp-57 is expressed in nerves from embryo day 12 to adult and is present in Schwann cell nuclei. To investigate whether Zfp-57 plays a role in myelination, Zfp-57 cDNA was overexpressed in Schwann cells. No effects were detected on Schwann cell differentiation towards a myelin phenotype, suggesting that Zfp-57 may not be involved in this process I undertook a detailed investigation of nerves of Krox-24 null mutant and heterozygous mice in which expression of the LacZ gene is controlled by the Krox-24 promoter. Krox-24 activation occurs in late embryonic/early postnatal peripheral nerve development. In nerves, mRNA levels of typical Schwann cell molecules are normal, proliferation and the ultrastructural morphology is not affected. In regenerating nerves Krox-24 deficient Schwann cells down-regulate myelin genes and up-regulate molecules required for regeneration as efficiently as wildtype cells except for p75NTR mRNA, which is increased in Krox-24 deficient mice. Furthermore axonal regeneration occurs normally. Schwann cell death occurs developmentally and the effect of Krox-24 deficiency on this phenomenon has been investigated using TUNEL. 1 day after transection of newborn sciatic nerves cell death is elevated threefold in Krox-24-/- mice compared to wiltype littermates. In a low density culture assay where cell death is measured in the absence of autocrine Schwann cell survival factors, there is no difference between Krox-24 null cells and normal Schwann cells. Additionally cell death induced by TGFβ is unaltered.
Type: | Thesis (Doctoral) |
---|---|
Qualification: | Ph.D |
Title: | Zinc-finger transcription factors in the Schwann cell lineage |
Open access status: | An open access version is available from UCL Discovery |
Language: | English |
Additional information: | Thesis digitised by ProQuest. |
Keywords: | Biological sciences; Schwann cells |
URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10103898 |
Archive Staff Only
![]() |
View Item |