Address of Corresponding Author

Cytogenet Genome Res 2006;112:16-22 (DOI: 10.1159/000087509)

  Abstract.

Mental retardation represents the more invalidating pathological aspect of trisomy 21 and has a hard impact on public health. The dosage imbalance of chromosome 21 genes could be the cause of neurological alterations and mental retardation seen in Down syndrome. We studied C21orf5 that we have demonstrated to be overexpressed in Down syndrome tissues, as a candidate gene for trisomy 21. A new optical technology (Rachidi et al., 2000) was used to compare signal intensity and cell density in presumptive embryonic brain compartments, at their boundaries and in higher specialized brain centres during fetal lifespan. We showed a developmentally regulated transcriptional activity of C21orf5 and a regional and cellular specific distribution of gene transcripts during human embryonic and fetal development. A wide but differential expression was detected in the nervous system during embryogenesis with a relatively lower level in the forebrain than in the midbrain and hindbrain and the highest transcription intensity in the future cerebellum. This developmentally regulated expression is maintained during post-embryogenesis and evolves selectively in fetal cerebral, hippocampal and cerebellar areas. Differential and cellular specificity were detected in hippocampus with higher C21orf5 mRNA level in the pyramidal cells compared to granular cells of the dentate gyrus. The expression pattern detected in cortical and cerebellar structures correlates well to the altered cortical lamination and to the lower size of the cerebellum observed in Down syndrome patients. In addition, the patterned differential expression detected in the medial temporal-lobe system, including hippocampal formation and perirhinal cortex, working as control centres of the memory circuits and involved in cognitive processes and memory storage, also corresponds to abnormal brain regions seen in Down syndrome patients. The C21orf5 selective expression in the key brain structures for learning and memory suggests that C21orf5 overexpression could participate in mental retardation pathogenesis in Down syndrome patients.   

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Request reprints from Mohammed Rachidi or Jean Maurice Delabar
EA 3508, Tour 54, E2-54-53, Case 7104, Université Denis Diderot
2 Place Jussieu, F-75251 Paris (France)
telephone: 33144275698; fax: 33144278338
e-mail: mrachidi@online.fr or delabar@paris7.jussieu.fr

  Article Information

Supported by EU contract QLRT-2001-00816, MENR and the Pasteur Institute.

M.R. and C.L. have contributed equally to this work.

Manuscript received 6 March 2005;
accepted in revised form for publication by B. Weber, 10 May 2005.
Number of Print Pages : 7
Number of Figures : 4, Number of Tables : 0, Number of References : 38