PMID- 8812055 OWN - NLM STAT- MEDLINE DCOM- 19961203 LR - 20250529 IS - 1044-7431 (Print) IS - 1044-7431 (Linking) VI - 7 IP - 1 DP - 1996 Jan TI - Expression patterns of two murine homologs of Drosophila single-minded suggest possible roles in embryonic patterning and in the pathogenesis of Down syndrome. PG - 1-16 AB - The single-minded (sim) gene encodes a transcriptional regulator that functions as a key determinant of central nervous system (CNS) midline development in Drosophila. We report here the identification of two murine homologs of sim, Sim1 and Sim2, whose products show a high degree of sequence conservation with Drosophila SIM in their amino-terminal halves, with each containing a basic helix-loop-helix domain as well as a PAS domain. Sim1 maps to the proximal region of mouse chromosome 10, whereas Sim2 maps to a portion of the distal end of chromosome 16 that is syntenic to the Down syndrome critical region of human chromosome 21. Recent exon-trapping studies have identified in the critical region several exons of a human sim homolog which appears to be the homolog of murine Sim2; this has led to the hypothesis that increased dosage of this sim homolog in cases of trisomy 21 might be a causal factor in the pathogenesis of Down syndrome. We have examined the expression patterns of the Sim genes during embryogenesis. Both genes are expressed in dynamic and selective fashion in specific neuromeric compartments of the developing forebrain, and the expression pattern of Sim2 provides evidence for early regionalization of the diencephalon prior to any overt morphological differentiation in this region. Outside the CNS, Sim1 is expressed in mesodermal and endodermal tissues, including developing somites, mesonephric duct, and foregut. Sim2 is expressed in facial and trunk cartilage, as well as trunk muscles. Both murine Sim genes are also expressed in the developing kidney. Our data suggest that the Sim genes play roles in directing the regionalization of tissues where they are expressed. Moreover, the expression pattern documented for Sim2 may provide insights into its potential roles in Down syndrome. FAU - Fan, C M AU - Fan CM AD - Department of Anatomy, University of California, San Francisco 94143-0452, USA. FAU - Kuwana, E AU - Kuwana E FAU - Bulfone, A AU - Bulfone A FAU - Fletcher, C F AU - Fletcher CF FAU - Copeland, N G AU - Copeland NG FAU - Jenkins, N A AU - Jenkins NA FAU - Crews, S AU - Crews S FAU - Martinez, S AU - Martinez S FAU - Puelles, L AU - Puelles L FAU - Rubenstein, J L AU - Rubenstein JL FAU - Tessier-Lavigne, M AU - Tessier-Lavigne M LA - eng SI - GENBANK/AF023864 SI - GENBANK/AF023865 SI - GENBANK/AF023866 SI - GENBANK/AF023867 SI - GENBANK/AF023868 SI - GENBANK/AF023869 SI - GENBANK/AF023870 SI - GENBANK/AF023871 SI - GENBANK/AF023872 SI - GENBANK/AF023873 SI - GENBANK/AF038853 SI - GENBANK/AF038854 SI - GENBANK/AF038855 SI - GENBANK/AF038856 SI - GENBANK/AF038857 SI - GENBANK/AF044913 GR - TGM94000/TI_/Telethon/Italy GR - TGM06S01/TI_/Telethon/Italy GR - R01 MH4942801/MH/NIMH NIH HHS/United States GR - R01 MH51561-01A1/MH/NIMH NIH HHS/United States GR - K02 MH01046-01/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Mol Cell Neurosci JT - Molecular and cellular neurosciences JID - 9100095 SB - IM EIN - Mol Cell Neurosci 1996 Jun;7(6):519 MH - Amino Acid Sequence MH - Animals MH - Brain/*metabolism MH - Down Syndrome/*genetics MH - Drosophila MH - Gene Expression/*genetics MH - In Situ Hybridization MH - Molecular Sequence Data EDAT- 1996/01/01 00:00 MHDA- 1996/01/01 00:01 CRDT- 1996/01/01 00:00 PHST- 1996/01/01 00:00 [pubmed] PHST- 1996/01/01 00:01 [medline] PHST- 1996/01/01 00:00 [entrez] AID - S1044-7431(96)90001-9 [pii] AID - 10.1006/mcne.1996.0001 [doi] PST - ppublish SO - Mol Cell Neurosci. 1996 Jan;7(1):1-16. doi: 10.1006/mcne.1996.0001.