GENE AND TRANSGENE REGULATION IN THE DEVELOPING MOUSE

小鼠LIM-同源框（Lhx）基因。 这个发展中的家庭 转录因子调节器官发生的重要步骤。 LHX2 和Lhx 7是一对密切相关的基因， 形成，特别是在发育中的中枢神经系统（CNS）。 对这两个基因的敲除分析正在进行中，以解决其 在中枢神经系统和其他地方的组合功能， 胚胎 Lhx 3和Lhx 4是另一对密切相关的基因， 负责腺垂体的形成，也起着 在运动神经元神经支配沿着脊髓， 目前正在通过双重功能丧失分析评估功能。 LIM结合蛋白。 我们已经分离出Ldb 1，一种新的因子， LIM基序存在于LIM同源结构域和LMO蛋白中。 合作 在Dawid博士的实验室中，我们已经证明了小鼠Ldb 1和 它的青蛙对应物XLdb 1与LIM同源框基因1协同作用， 诱导发育早期决定因素，并形成次级轴， 注入青蛙胚胎中。 胶质细胞源性神经营养因子（GDNF）作为一种神经营养因子被分离出来。 中脑多巴胺能神经元的神经营养因子。 鉴于其 体外对多种神经元群体的神经营养活性 在体内，GDNF被认为是一种潜在的治疗剂， 治疗神经紊乱 在哺乳动物的发育过程中，GDNF 不仅在神经系统中， 后肾肾和胃肠道，表明 在器官形成过程中的可能功能。 我们调查了 GDNF在发育过程中通过在小鼠中产生无效突变来表达， GDNF基因座。与Hoffer博士、Saarma博士和 Sariola我们能够证明突变小鼠显示肾脏 发育不全或发育不全以及肠神经支配缺陷。 GDNF诱导 后肾发育过程中输尿管芽的形成和分支。 在 此外，该因子对于正常的神经支配是必不可少的。 胃肠道

Murine LIM-homeobox (Lhx) genes. This family of developmental transcription factors regulates important steps of organogenesis. Lhx2 and Lhx7, a pair of closely related genes, are essential for pattern formation, particularly in the developing central nervous system (CNS). Knockout analyses of these two genes are in progress to address their combinatorial functions in the CNS and elsewhere in the developing embryo. Lhx3 and Lhx4, another closely related pair of genes, is responsible for the formation of the adenohypophysis, and also plays an essential role in motoneuron innervation along the spinal chord, a function currently being assessed via double loss-of-function analysis. LIM-binding proteins. We have isolated Ldb1, a novel factor that binds LIM motifs present in LIM-homeodomain and LMO proteins. In collaboration with the laboratory of Dr. Dawid , we have shown that the murine Ldb1 and its frog counterpart XLdb1 synergize with the LIM-homeobox gene 1 to induce early determinators of development and to form secondary axes when injected in frog embryos. Glial cell line-derived neurotrophic factor (GDNF) was isolated as a neurotrophic factor for midbrain dopaminergic neurons. In view of its neurotrophic activity on a wide range of neuronal populations in vitro and in vivo, GDNF is being considered as a potential therapeutic agent for neuronal disorders. During mammalian development, GDNF is expressed not only in the nervous system, but also very prominently in the metanephric kidney and in the gastrointestinal tract, suggesting possible functions during organogenesis. We have investigated the role of GDNF during development by generating a null mutation in the murine GDNF locus. Together with the laboratories of Drs. Hoffer, Saarma and Sariola we were able to demonstrate that mutant mice show kidney agenesis or dysgenesis and defective enteric innervation. GDNF induces ureter bud formation and branching during metanephros development. In addition, the factor is essential for proper innervation of the gastrointestinal tract.