GENETIC ANALYSIS OF MYOGENIC CELL DETERMINATION

当代生物学研究中的一项主要努力是识别基因座 它们控制着发展的决定。此外，风吹草动， 正常的分化过程可能有助于肿瘤的发生。 确定涉及产生和 保持差异化状态对于理解两者都很重要 正常发育和疾病。 这是一项研究细胞类型确定的控制的建议 在哺乳动物细胞中。通过利用体外培养的成肌细胞系，以及 体细胞和分子遗传学相结合的方法，调节 MyoD家族的生肌调节基因将被分析。 将检测类型间杂交种的激活和抑制 肌肉发生。这种性质的基因研究已经被用来 在以下几个方面确定积极和消极的监管互动 实验系统。 该项目有四个目标：1)明确负面监管的作用 10T1/2X成纤维细胞杂交中的MyoD，2)确定是否有额外的 成纤维细胞染色体激活肌肉、脂肪或软骨表型 1OT1/2细胞，3)确定MyoD是在顺式还是反式中被抑制 和4)研究1OT1/2细胞灭绝的遗传基础 X个L6成肌细胞杂交种。通过识别并最终隔离这些 独特的调节器，我们可以开始定义涉及的遗传机制 在肌肉细胞的测定和分化中。一个 对控制肌原的调节回路的理解 谱系将对基因的扰动提供重要的见解 导致肌肉发育异常和肿瘤形成的表达。

A major effort in contemporary biological research is to identify loci that control developmental decisions. In addition, disturbance of the normal differentiation process can contribute to tumorigenesis. Determining the key regulatory mechanisms involved in generating and maintaining the differentiated state is important for understanding both normal development and disease. This is a proposal to investigate the control of cell type determination in mammalian cells. By utilizing myoblast cell lines grown in vitro, and a combined somatic cell and molecular genetic approach, the regulation of the MyoD family of myogenic regulatory genes will be analyzed. Intertypic hybrids will be assayed for activation and repression of myogenesis. Genetic studies of this nature have been utilized to identify positive and negative regulatory interactions in a number of experimental systems. This project has four goals: 1) define the role of negative regulation of MyoD in 10T1/2 X fibroblast hybrids, 2) determine whether additional fibroblast chromosomes activate muscle, fat, or cartilage phenotypes in 1OT1/2 cells, 3) determine whether MyoD is repressed in cis or in trans in 1OT1/2 cells, and 4) examine the genetic basis of extinction in 1OT1/2 X L6 myoblast hybrids. By identifying and ultimately isolating these unique regulators, we can begin to define the genetic mechanisms involved in the determination and differentiation of muscle cells. An understanding of the regulatory circuits which control the myogenic lineage will give important insights into the perturbations of gene expression that result in abnormal muscle development and tumorigenesis.