Bosnakovski, Darko (2015) DUX4, a gene involved in Facioscapulohumeral muscular dystrophy (FSHD), most likely plays a role in early neurogenesis. In: GlowBrain Workshop “Visualization of molecular markers in the brain”, University of Zagreb School of Medicine, Croatian Institute for Brain research.
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Abstract
Facioscapulohumeral muscular dystrophy (FSHD) is neuromuscular disorder connected with deletion of D4Z4 repeats in subtelomeric region on chromosome 4. Molecular mechanism of the disease is still unknown. However, misexpression of the double homeodomain protein DUX4 which is localized in each of D4Z4 repeats is believed to play a role in FSHD. DUX4 expressed in myoblasts at low levels blocks myotube formations and displays competitive interactions with both PAX3 and PAX7. This is most likely due to DUX4 homeodomains similarity in sequence to PAX3, PAX6, and PAX7. On the other hand, the normal function of DUX4 remains mysterious. The mouse has a homologue named Dux that is expressed in various tissues, but most prominently in neurogenic tissues. In addition, expression of DUX4 has been reported in human testis, human ES cells and pluripotent cells. To test the effect of DUX4 in early stage of development we generated DUX4 inducible system in murine embryonic stem cell. We found that expression of even low levels of DUX4 is incompatible with pluripotency. Transcriptional profiling revealed that rather than a germ lineage program, DUX4 induced a neurectodermal program. Embryoid bodies exposed to a pulse of DUX4 expression displayed severely inhibited mesodermal differentiation, but acquired neurogenic potential and formation of TuJ1+ neurons.
| Item Type: | Conference or Workshop Item (Speech) |
|---|---|
| Subjects: | Medical and Health Sciences > Basic medicine |
| Divisions: | Faculty of Medical Science |
| Depositing User: | Darko Bosnakovski |
| Date Deposited: | 19 Mar 2018 12:13 |
| Last Modified: | 19 Mar 2018 12:13 |
| URI: | https://eprints.ugd.edu.mk/id/eprint/19734 |
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