Down syndrome-critical region contains a gene homologous to Drosophila sim expressed during rat and human central nervous system development.

Dahmane, Nadia; Charron, Gisele; Lopes, Carmela; Yaspo, Marie–Laure; Maunoury, Catherine; Decorte, Laurence; Sinet, Pierre-Marie; Bloch, Bertrand; Delabar, Jean–Maurice

doi:10.1073/pnas.92.20.9191

Cited by 86 publications

(41 citation statements)

References 24 publications

(29 reference statements)

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“…These zones of expression include the longitudinal basal plate of the diencephalon (Sim1 and Sim2), the mesencephalon (Sim1), the zona limitans intrathalamica (Sim1 and Sim2) and the portion of the spinal cord that flanks the floor plate (Sim1) (Ema et al, 1996a;Ema et al, 1996b;Fan et al, 1996). Sim2 maps to the region responsible for Down Syndrome (DS) on Chromosome 21 (Chrast et al, 1997;Dahmane et al, 1995;Muenke et al, 1995). Interestingly, Sim2 is also expressed in non-neuronal tissues, including branchial arches and the developing limb, which are primordia of tissues and organs where DS abnormalities are frequently observed (Rachidi et al, 2005).…”

Section: Research Articlementioning

confidence: 99%

The highly ordered assembly of retinal axons and their synaptic partners is regulated by Hedgehog/Single-minded in theDrosophilavisual system

et al. 2006

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During development of the Drosophila visual center, photoreceptor cells extend their axons (R axons) to the lamina ganglion layer, and trigger proliferation and differentiation of synaptic partners (lamina neurons) by delivering the inductive signal Hedgehog (Hh). This inductive mechanism helps to establish an orderly arrangement of connections between the R axons and lamina neurons, termed a retinotopic map because it results in positioning the lamina neurons in close vicinity to the corresponding R axons. We found that the bHLH-PAS transcription factor Single-minded (Sim) is induced by Hh in the lamina neurons and is required for the association of lamina neurons with R axons. In sim mutant brains, lamina neurons undergo the first step of differentiation but fail to associate with R axons. As a result, lamina neurons are set aside from R axons. The data reveal a novel mechanism for regulation of the interaction between axons and neuronal cell bodies that establishes precise neuronal networks.

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Section: Research Articlementioning

confidence: 99%

The highly ordered assembly of retinal axons and their synaptic partners is regulated by Hedgehog/Single-minded in theDrosophilavisual system

et al. 2006

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“…Sim1 maps on mouse chromosome 10 and Sim2 on mouse chromosome 16 in a region of synteny with HC21 (Fan et al 1996). Both mouse Sim1 and Sim2 genes are expressed early [Sim2 from embryonic day 8.0 (E8.0) and Sim1 from E9.0] in developing forebrain (Ema et al 1996b;Fan et al 1996;Moffett et al 1996;Yamaki et al 1996) and outside the central nervous system (CNS), in somites, mesonephric duct, and foregut (Sim1), in facial and trunk cartilage, trunk muscles (Sim2), and in the developing kidney (Sim1 and Sim2) (Dahmane et al 1995;Ema et al 1996b;Fan et al 1996;Moffett et al 1996). In adult mouse, both Sim1 and Sim2 are expressed in kidney and skeletal muscles, whereas Sim2 is also expressed in the lung (Ema et al 1996a,b;Moffett et al 1996).…”

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confidence: 99%

Cloning of Two Human Homologs of the Drosophila single-minded Gene SIM1 on Chromosome 6q and SIM2 on 21q Within the Down Syndrome Chromosomal Region

Chrast¹,

Scott²,

Chen³

et al. 1997

Genome Res.

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As part of our effort to clone genes of human chromosome 21 that may contribute to Down syndrome, we have previously isolated four exons with homology to Drosophila single-minded (sim) gene, which encodes a transcription factor that is a master regulator of fruit fly neurogenesis. These exons were used to clone and characterize two human homologs of the Drosophila sim gene, SIM1 and SIM2, which map to chromosomes 6q16.3-q21 and 21q22.2, respectively; SIM2 maps within the so-called Down syndrome chromosomal region. Recently, two mouse homologs, Sim1 and Sim2, also have been identified. There is a high level of homology among human, mouse, and Drosophila sim genes in their amino-terminal half where the conserved bHLH, PAS1, PAS2, and HST domains are present. In contrast, the carboxy-terminal parts are only homologous between SIM1 and Sim1 and SIM2 and Sim2. Two isoforms (SIM2 and SIM2s) of human SIM2 have been detected that differ in their 3Ј ends. Northern blot analysis revealed one mRNA SIM1 species of ∼9.5 kb and four different mRNA SIM2 species of 2.7, 3, 4.4, and 6 kb in human fetal kidney. The function of both human SIM1 and SIM2 is unknown. However, three copies of SIM2 may contribute to some specific Down syndrome phenotypes because of (1) mapping position, (2) potential function as transcriptional repressor, (3) likely dimerization with other transcription factors, (4) the temporal and spatial expression pattern of mouse Sim2, and (5) the potentially analogous role of human SIM2 to that of Drosophila sim during neurogenesis.

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“…Despite their seemingly different transcriptional roles, the expression patterns of murine Sim genes during development are reminiscent of those of the Drosophila sim (Dahmane 1995;Ema et al 1996;Fan et al 1996;Yamaki et al 1996). For example, Figure 1 shows that the Drosophila sim transcript and protein are detected in the CNS midline cells located in the ventral body wall.…”

mentioning

confidence: 97%

“…Several laboratories have characterized and cloned the DSCR. Using the exon-trapping technique to isolate potential coding sequences within this region, two groups have identified exons that predict an open reading frame that is highly homologous to the Drosophila sim gene product (Chen et al 1995;Dahmane et al 1995). In parallel, two murine homologs of sim have been cloned and named Sim1 and Sim2 (Ema et al 1996;Fan et al 1996;Moffett et al 1996;Yamaki et al 1996).…”

mentioning

confidence: 99%

Single-minded—Two Genes, Three Chromosomes : Figure 1.

Michaud¹,

Fan²

1997

Genome Res.

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Down syndrome-critical region contains a gene homologous to Drosophila sim expressed during rat and human central nervous system development.

Abstract: ABSTRACT

Cited by 86 publications

References 24 publications

The highly ordered assembly of retinal axons and their synaptic partners is regulated by Hedgehog/Single-minded in theDrosophilavisual system

The highly ordered assembly of retinal axons and their synaptic partners is regulated by Hedgehog/Single-minded in theDrosophilavisual system

Cloning of Two Human Homologs of the Drosophila single-minded Gene SIM1 on Chromosome 6q and SIM2 on 21q Within the Down Syndrome Chromosomal Region

Single-minded—Two Genes, Three Chromosomes : Figure 1.

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