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

妊娠中后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。通过小鼠胚胎显微注射和体外发育系统，结合基因敲除和其他转基因小鼠以及体外实验，检测了白血病抑制因子(LIF)、瘦素(Leptin)、促肾上腺皮质激素(ACTH)以及其他可能在网络中发挥作用的相关体液因子如NPY和GM-CSF在胚胎脑和其他器官中的作用。LIF和Leptin在脑组织发生中的新作用已被阐明，ACTH对多个器官的产前效应已被提出。对胚胎血清、脑脊液和羊水中的LIF等体液因子进行了定量分析，并观察其水平与器官发育的关系。为了进一步综合分析多个器官的“协调”发育与每个器官的组织发生的关系，我们开始利用数学方法。对人胎儿脑桥、人胚胎和胎儿身体部位的发育特征进行了测量和分析。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，通过将胚胎移植到非肥胖糖尿病(NOD)小鼠和其他品系小鼠之间，对非肥胖糖尿病(NOD)小鼠进行了分析。

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.