Developmental analysis of neuro-immuno-endocirne network and harmonized histogenesis of organs

神经-免疫-内分泌网络和器官协调组织发生的发育分析

• 批准号: 15209034
• 负责人: OTANI Hiroki
• 金额: $ 32.2万
• 依托单位: Shimane University (2004-2006)Shimane Medical University (2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15209034/
• 关键词: Neuro-immuno-endocirne network; histogenesis; mouse embryo; exo utero; leukemia inhibitory factor; adrenocorticotropic hormone; leptin; NPY; ELISA; gp130; FGF

Histogenesis of organs during mid-to late-gestation and early years after birth creates the basis of organ functions that work for whole life period, and thus variations in organ histogenesis are deeply related with predisposition of diseases involving these organs. In this study, we analyzed the development of neuro-immuno-endocrine network and its possible role in the 'harmonized' histogenesis of organs. By micro-injection and exo utero development system in mouse embryos, together with use of knockout and other genetically modified mice as well as in vitro experiments, effects of leukemia inhibitory factor (LIF), leptin, adrenocorticotropic hormone (ACTH), and other related humoral factors such as NPY and GM-CSF that are supposed to work in the network were examined in the brain and other organs of embryos. Novel roles of LIF and leptin have been elucidated in the cerebral histogenesis, and prenatal effects of ACTH on multiple organs have been suggested. LIF and other humoral factors were quantitatively analyzed in the serum, cerebrospinal fluid, and amniotic fluid of the embryo, and their levels were observed to change in relation to the development of organs. To further comprehensively analyze the 'harmonized' development of multiple organs in relation to histogenesis of each organ, we started to utilize mathematical methods. The pons in human fetuses and body parts of human embryos and fetuses were measured and analyzed with regard to developmental features. Also to analyze the possible effect of maternal environmental factors on histogenesis and predisposition of disease, non-obese diabetic (NOD) mice, an animal model of human type 1 diabetes, were analyzed by transferring embryos between NOD and other strain mice.

妊娠中晚期和出生后早期器官的组织发生为整个生命周期的器官功能奠定了基础，因此器官组织发生的变化与涉及这些器官的疾病的易感性密切相关。在这项研究中，我们分析了神经-免疫-内分泌网络的发展及其在器官“协调”组织发生中的可能作用。通过小鼠胚胎的显微注射和子宫外发育系统，结合基因敲除和其他遗传修饰小鼠以及体外实验，研究了白血病抑制因子（LIF）、瘦素（leptin）、促肾上腺皮质激素（ACTH）以及其他相关的体液因子如NPY和GM-CSF在胚胎脑和其他器官中的作用。已阐明了LIF和瘦素在脑组织发生中的新作用，并提出了ACTH对多个器官的产前影响。LIF和其他体液因子在胚胎的血清、脑脊液和羊水中进行了定量分析，并观察到它们的水平随器官发育而变化。为了进一步全面分析多个器官的“协调”发展与每个器官的组织发生的关系，我们开始利用数学方法。对人胚胎脑桥及人胚胎和胎儿的身体部位进行了测量和分析。为了分析母体环境因素对组织发生和疾病易感性的可能影响，通过在NOD和其他品系小鼠之间移植胚胎来分析非肥胖糖尿病（NOD）小鼠（人类1型糖尿病的动物模型）。

项目成果

Basement membrane fragility underlies embryonic lethality in fukutin-nul mice.

基底膜脆性是 fukutin-nul 小鼠胚胎致死的基础。

• 发表时间: 2005
• 期刊: Neurobiology of Disease 19
• 作者: Yoshioka J;Node K;Hasegawa S;Hori M;Nishimura T 他5名.;Hiroki Kurahashi
• 通讯作者: Hiroki Kurahashi

Maternal environment affects endogenous virus induction in the offspring of NOD mice.

母体环境影响 NOD 小鼠后代内源病毒的诱导。

• 发表时间: 2005
• 期刊: Congenital Anomalies 45
• 作者: Y.Kagohashi

汎用的高感度ELISA法およびその試薬キット

通用型高灵敏度ELISA方法及其试剂盒

• 发表时间: 2007

Leptin affects oligodendroglial development in the mouse embryonic cerebral cortex.

• 发表时间: 2006-02
• 期刊: Neuro endocrinology letters
• 作者: J. Udagawa;M. Nimura;H. Otani

Gi2 Signaling Enhances Proliferation of Neural Progenitor Cells in the Developing Brain*

• DOI: 10.1074/jbc.m406721200
• 发表时间: 2004-09
• 期刊: Journal of Biological Chemistry
• 影响因子: 4.8
• 作者: H. Shinohara;J. Udagawa;R. Morishita;H. Ueda;H. Otani;R. Semba;Kanefusa Kato;T. Asano