Expression patterns of two murine homologs of Drosophila single-minded suggest possible roles in embryonic patterning and in the pathogenesis of down syndrome
Expression patterns of two murine homologs of Drosophila single-minded suggest possible roles in embryonic patterning and in the pathogenesis of down syndrome
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DOI：
10.1006/mcne.1996.0001
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发表时间：
1996-01-01
影响因子：
3.5
通讯作者：
TessierLavigne, M
中科院分区：
文献类型：
--
作者：
Fan, CM;Kuwana, E;TessierLavigne, M
一心一意的(sim)基因编码一个转录监管机构作为中枢神经系统(CNS)的一个关键决定因素中线果蝇发展,我们报告两个sim的小鼠同源染色体的识别,Sim1和Sim2的产品序列表现出高度的保护与果蝇sim伴部分,每个包含一个基本helix-loop-helix域以及不是域,Sim1映射到鼠标的近端地区10号染色体而Sim2则定位于16号染色体远端与人类21号染色体唐氏综合症关键区域相同的部分。最近的外显子捕获研究已经在关键区域发现了人类sim同源的几个外显子，这些外显子似乎与小鼠Sim2同源；这导致了一种假设，即在21三体病例中增加这种sim同源物的剂量可能是唐氏综合征发病的一个原因。我们研究了胚胎发生过程中sim基因的表达模式。这两个基因都在发育中的前脑的特定神经区室中以动态和选择性的方式表达，Sima的表达模式为间脑的早期区域化提供了证据，该区域在任何明显的形态分化之前。在中枢神经系统之外，Sim1表达于中胚层和内胚层组织，包括发育中的体、中肾管和前肠，Sim2表达于面部和躯干软骨以及躯干肌肉。两种小鼠的Sim基因也在发育中的肾脏中表达，我们的数据表明Sim基因在指导其表达的组织区域化中发挥作用，此外，记录的Sima表达模式可能为其在唐氏综合症中的潜在作用提供见解。
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 Sima 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 Sima may provide insights into its potential roles in Down syndrome.