Development of Cardiovascular Regulatory Mechanisms: Exploring the Early Embryonic Frontier II

项目总结-0614815本项目的长期目标是了解生理过程的调节如何与脊椎动物胚胎的发育过程相结合。重点是早期胚胎发育，这是既没有充分研究和了解甚少。 三个研究目标整合了创新的发育生理学实验的心血管系统的鸟类模型胚胎（鸡，鸸鹋）连同多方面的研究培训，包括研究生和本科生与初中和高中教师和学生合作。 具体而言，本项目的目标是：1）确定早期胚胎心血管调节的发育。 据推测，内在的心脏机制（肌肉长度-张力关系），与血管自动调节（在局部水平控制血管的收缩和扩张），必须负责早期胚胎血压和流量的任何调节。为了检验这一假设，将在血容量负荷期间进行血压和流量的体内测量，以及血管活性物质和氧水平的影响的测量，将用于确定调节的发育开始。 . 2)血容量调节的发展探讨。 第二个假设是，血容量最初调节不良，直到神经和/或神经调节的心血管和肾脏机制充分发展。鸟类胚胎中的液体平衡将通过血室负荷和损失受到挑战。 然后将测量血压、心率、红细胞数量、水从血管中的运输和血容量，以确定代偿机制的发育开始。 3)教师生理学教育计划的扩展。 PI新成立的科学和数学高级研究技术（SMART）计划将高度积极的高中教师暴露在PI实验室的当代研究中。在与UNT的艺术和科学以及教育领域的科学教育学教师的密切合作下，该计划将扩展到高中以外，包括中学教师，并将使用更先进的评估工具来评估计划校友的绩效改进（例如提高学生的标准化考试成绩和学生提前安置课程的入学率）。这些研究将在三个领域作出重要的科学贡献。 1)关于脊椎动物胚胎如何生理发育的信息很少。这些测量将提供关于早期胚胎心血管系统（CVS）个体发育的重要的、基于机械的信息，提高对心血管调节如何受到器官发生和胚胎生长期间发育过程的影响并与之整合的理解。 2)这些信息将使CVS表型可塑性的更好的解释，并产生更好的理解的现象“胎儿编程”。 3)在为人类胎儿甚至胚胎的先天性缺陷创造矫正程序之前，加强对脊椎动物胚胎生理学的理解至关重要。更广泛的社会影响：除了培训本科生，研究生和博士后，SMART计划通过包括初中和高中学生整合了研究和教育。 SMART在UNT的生理学实验室从事科学学校教师的原始生理学研究。据推测，这些教师然后把他们的经验传授给他们的学生，提高了对科学的热爱和迷恋。 德克萨斯州不再有单一的多数人口，使PI的实验室能够指导少数民族的研究生和本科生（PI的实验室人员中有50%由NSF鼓励的少数民族组成）。 最后，将继续开发NSF支持的发育生理学社区网站，为特定群体（例如本科生）创建资源部分。 作为一个进一步的推广机制，具体的网络材料将创建illustrat向外行公众为什么发育生理学是一个重要的NSF目标funding.In总结，这个持续的研究计划将提高胚胎生理学的理解，产生新的见解发育进化生物学，通过博士后研究员为本科生提供当代的培训机会，并为在校学生创造发现的机会。

PROJECT SUMMARY - 0614815The long-term goal of this program is to understand how regulation of physiological processes is integrated together with developmental processes in vertebrate embryos. Emphasis is on early embryonic development, which is both inadequately studied and poorly understood. Three research objectives integrate innovative developmental physiology experiments on the cardiovascular system of bird model embryos (chicken, emu) together with multi-faceted research training comprising graduate and undergraduate students collaborating with middle and high school teachers and their pupils. Specifically the aims of this project are:1) Determination of the Development of Early Embryonic Cardiovascular Regulation. It is hypothesized that intrinsic cardiac mechanisms (muscle length-tension relationships), in concert with vascular autoregulation (constriction and dilation of blood vessels controlled at the local level), must be responsible for any regulation of early embryonic blood pressure and flow. To test this hypothesis, in vivo measurements of blood pressures and flows will be made during blood volume loading, as well as measurements of the effects of vasoactive substances and oxygen levels, will be used to determine the developmental onset of regulation. . 2) Exploration of the Development of Blood Volume Regulation. As second hypothesis is that blood volume is initially poorly regulated until neurally and/or hormonally regulated cardiovascular and renal mechanisms develop sufficiently. Fluid balance in bird embryos will be challenged through blood compartment loading and loss. Blood pressure, heart rate, red blood cell numbers, water transport out of the vessels and blood volume will then be measured to determine the developmental onset of compensatory mechanisms. 3) Expansion of Teacher Physiology Education Program. The PI's newly established Science and Math Advanced Research Techniques (SMART) program exposes highly motivated high school teachers to contemporary research in the PI's lab. In close collaboration with UNT's science pedagogy faculty in Arts and Sciences and in Education, this program will be expanded beyond high school to include middle school teachers, and will use more advanced assessment tools for evaluating performance improvement in program alumni (e.g. improved standardized student test scores and student advance placement course enrollment).Intellectual Merit: Key scientific contributions will emerge from these studies in three areas. 1) Little information exists on how vertebrate embryos develop physiologically. These measurements will provide vital, mechanistically-based information on the ontogeny of the early embryonic cardiovascular system (CVS), improving understanding of how cardiovascular regulation is affected by, and integrated with, developmental processes during organogenesis and embryonic growth. 2) This information will enable better interpretation of CVS phenotypic plasticity and yield greater understanding of the phenomenon of "fetal programming". 3) Enhanced understanding of embryonic physiology in vertebrates is vital prior to creating corrective procedures for congenital defects in the human fetus and even embryos. Broader Societal Impact: In addition to training undergraduates, graduates and post-docs, the SMART Program integrates research and education by including middle as well as high school students. SMART engages science school teachers in original physiology research in UNT's physiology laboratories. It is hypothesized that these teachers then impart their experience to their students, enhancing a love and fascination for science. Texas no longer has a single majority population, enabling the PI's lab to mentor minority graduate and undergrad students (50% of the PI's lab personnel consist of minorities encouraged by NSF). Finally, development will continue for the NSF-supported Developmental Physiology community website by creating resource sections for specific cohorts (e.g. undergrads). As a further outreach mechanism, specific web material will be created to illustrat to the lay public why developmental physiology is an important NSF target for funding.In summary, this continuing research program will enhance understanding of embryonic physiology, yield new insights into developmental evolutionary biology, provide contemporary training opportunities for undergrads through post-doctoral fellows, and create discovery opportunities for school students.