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

这个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，这方面的研究不够充分，了解也很少。三个研究目标结合了鸟类模型胚胎（鸡、鸸鹋）心血管系统的创新发育生理学实验，以及研究生和本科生与初中和高中教师及其学生合作的多方面研究训练。具体而言，该项目的目的是：1)确定早期胚胎心血管调节的发展。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（局部水平控制的血管收缩和扩张）一致，必须负责早期胚胎血压和血流的任何调节。为了验证这一假设，将在血容量负荷期间进行体内血压和血流测量，以及血管活性物质和氧气水平的影响测量，以确定发育调节的开始。2)血容量调节的发展探索。第二个假设是，在神经和/或激素调节的心血管和肾脏机制充分发育之前，血容量最初的调节很差。鸟类胚胎中的液体平衡将通过血室的负荷和损失而受到挑战。然后测量血压、心率、红细胞数量、血管外水运输和血容量，以确定代偿机制的发育开始。3)教师生理学教育项目的拓展。PI新成立的科学和数学高级研究技术（SMART）项目让积极性很高的高中教师在PI实验室中参与当代研究。通过与UNT的文理和教育学科的科学教育学教师的密切合作，该项目将从高中扩展到中学教师，并将使用更先进的评估工具来评估项目校友的表现改善（例如提高标准化学生考试成绩和学生先修课程的入学率）。智力价值：这些研究将在三个领域产生关键的科学贡献。关于脊椎动物胚胎生理发育的信息很少。这些测量将为早期胚胎心血管系统（CVS）的个体发生提供重要的、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发育过程的影响和整合的理解。2)这些信息将有助于更好地解释CVS表型可塑性，并对“胎儿编程”现象有更深入的了解。3)在为人类胎儿甚至胚胎的先天性缺陷制定矫正程序之前，加强对脊椎动物胚胎生理学的了解至关重要。更广泛的社会影响：除了培养本科生、毕业生和博士后外，SMART计划还通过包括中学生和高中生在内的研究和教育相结合。SMART聘请理学院教师在UNT的生理学实验室进行原始生理学研究。据推测，这些教师随后将他们的经验传授给学生，增强他们对科学的热爱和迷恋。德克萨斯州不再是单一的多数人口，这使得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%是由NSF鼓励的少数民族组成的）。最后，nsf支持的发育生理学社区网站将继续发展，为特定人群（如本科生）创建资源部分。作为进一步的推广机制，将创建特定的网络材料，向非专业公众说明为什么发育生理学是NSF重要的资助目标。总之，这个持续的研究项目将加强对胚胎生理学的理解，产生对发育进化生物学的新见解，通过博士后研究员为本科生提供当代培训机会，并为在校学生创造发现机会。

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.