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Int J Dev Neurosci. 2005 Aug;23(5):475-84.

Spatial and temporal localization during embryonic and fetal human development of the transcription factor SIM2 in brain regions altered in Down syndrome.

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  • 1EA 3508, Tour 54, E2-54-53, Case 7104, Universit√© Denis Diderot, 2 Place Jussieu, 75251 Paris, France. mrachidi@9online.fr

Abstract

Human SIM2 is the ortholog of Drosophila single-minded (sim), a master regulator of neurogenesis and transcriptional factor controlling midline cell fate determination. We previously localized SIM2 in a chromosome 21 critical region for Down syndrome (DS). Here, we studied SIM2 gene using a new approach to provide insights in understanding of its potential role in human development. For the first time, we showed SIM2 spatial and temporal expression pattern during human central nervous system (CNS) development, from embryonic to fetal stages. Additional investigations were performed using a new optic microscopy technology to compare signal intensity and cell density [M. Rachidi, C. Lopes, S. Gassanova, P.M. Sinet, M. Vekemans, T. Attie, A.L. Delezoide, J.M. Delabar, Regional and cellular specificity of the expression of TPRD, the tetratricopeptide Down syndrome gene, during human embryonic development, Mech. Dev. 93 (2000) 189--193]. In embryonic stages, SIM2 was identified predominantly in restricted regions of CNS, in ventral part of D1/D2 diencephalic neuroepithelium, along the neural tube and in a few cell subsets of dorsal root ganglia. In fetal stages, SIM2 showed differential expression in pyramidal and granular cell layers of hippocampal formation, in cortical cells and in cerebellar external granular and Purkinje cell layers. SIM2 expression in embryonic and fetal brain could suggest a potential role in human CNS development, in agreement with Drosophila and mouse Sim mutant phenotypes and with the conservation of the Sim function in CNS development from Drosophila to Human. SIM2 expression in human fetal brain regions, which correspond to key structures for cognitive processes, correlates well with the behavioral phenotypes of Drosophila Sim mutants and transgenic mice overexpressing Sim2. In addition, SIM2-expressing brain regions correspond to the altered structures in DS patients. All together, these findings suggest a potential role of SIM2 in CNS development and indicate that SIM2 overexpression could participate to the pathogenesis of mental retardation in Down syndrome patients.

PMID:
15946822
[PubMed - indexed for MEDLINE]
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