TY - JOUR
T1 - Expression patterns of two murine homologs of Drosophila single-minded suggest possible roles in embryonic patterning and in the pathogenesis of Down syndrome
AU - Fan, Chen Ming
AU - Kuwana, Ellen
AU - Bulfone, Alessandro
AU - Fletcher, Colin F.
AU - Copeland, Neal G.
AU - Jenkins, Nancy A.
AU - Crews, Stephen
AU - Martinez, Salvador
AU - Puelles, Luis
AU - Rubenstein, John L.R.
AU - Tessier-Lavigne, Marc
N1 - Funding Information:
We thank T. Jessell, M. Placzek, and G. Martin for helpful comments on an early version of this manuscript, D. J. Gilbert for excellent technical assistance, and Drs. A. Klar, A. Joyner, and F. Perrin-Schmidt for the Fspondin, En1, and Mtwist cDNAs, respectively. This work was supported by grants to M.T.L. from the Lucille P. Markey Charitable Trust and the Human Frontiers Science Program (Grant RG41/95), and by the Howard Hughes Medical Institute. C.-M. Fan was supported by postdoctoral fellowships from the Damon Runyon±Walter Winchell Cancer Research Fund, the American Cancer Society, California Division, and the Howard Hughes Medical Institute. This work was also supported by grants to J.L.R.R. (Human Frontiers Science Program Grant RG41/95, March of Dimes, NARSAD, the John Merck Fund, P®zer Pharmaceuticals, and NIMH RO1 MH49428-01, NIMH RO1 MH51561-01A1, and K02 MH01046-01) and, in part, by the National Cancer Institute, DHHS, under contract with ABL. M.T.L. is an Assistant Investigator of the Howard Hughes Medical Institute.
PY - 1996/1
Y1 - 1996/1
N2 - 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 situ homolog which appears to be the homolog of murine Sim2; this has led to the hypothesis that increased dosage of this situ 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.
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 situ homolog which appears to be the homolog of murine Sim2; this has led to the hypothesis that increased dosage of this situ 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.
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U2 - 10.1006/mcne.1996.0001
DO - 10.1006/mcne.1996.0001
M3 - Article
C2 - 8812055
AN - SCOPUS:0029968399
SN - 1044-7431
VL - 7
SP - 1
EP - 16
JO - Molecular and Cellular Neurosciences
JF - Molecular and Cellular Neurosciences
IS - 1
ER -