Embryonic Transitions in Vertebrate Cardiovascular Physiology - II

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This award will extend our current highly limited understanding of the development of cardiovascular regulation, and its potential plasticity in vertebrate embryos. The four-year project will focus on three areas of study, using conventional developmental models (the fry of zebrafish Brachydanio rerio, embryos of chickens Gallus gallus), as well as embryos of other fishes and birds. The first area extends the PI's investigation of the development of the circulation and its regulation in early vertebrate embryos, making quantitative measurements of blood pressure, blood flow, and heart rate as a function of development, and during pharmacological and environmental manipulation. In particular, these studies will focus on two aims: 1) Determination of changes in cardiovascular regulation during embryonic development. Recent findings show that there are non-linear rates of both appearance and maturation in the development of reflexes controlling the circulation. Major species-specific differences are emerging between chicken, emu and zebrafish embryos. Thus experiments to determine whether the venerable chick embryo model is indeed representative of vertebrate physiological development are warranted. 2) Quantification of the specific properties of the blood vessels of the avian chorioallantoic membrane (CAM), which remains largely a physiological black box. Because the CAM and embryonic vessels are located in series, intrinsic responses of the vascular beds of the embryo could be muted or completely masked by qualitatively different vessel diameter responses occurring simultaneously in the CAM per se, especially when blood pressure and other measurements are made at only one point in the circulation.The second area focuses on the breathing transition in late incubation of the avian embryo as it internally pips (pushes its beak into the internal air cell) and relinquishes respiration using the CAM for respiration using the lungs. This award will fund experiments to characterize the physiological changes that occur from day 19-21 in chick embryos, and from Day 50-53 in emu embryos. The PI's experiments to date suggest that this 2-3 day period holds intense and complex change for cardiovascular regulation, and its relatively slow time course relative to mammalian birth should provide critical new insights in cardio-pulmonary transitions.The third area will be an investigation of how environment (e.g. hypoxia) influences normal developmental trajectories for the cardiovascular system. In particular, planned experiments will explore the extent to which embryonic cardiovascular systems exhibit "self-repair" as development progresses. Exciting new results suggest that embryos with modifications of metabolism in early development produced by low environmental oxygen can develop along unexpected trajectories and still arrive at a normal metabolic state.The proposed research program will make important and timely contributions to scientific advancement and human resource development. The proposed measurements will provide mechanistically-based information on how cardiovascular systems develop, how they respond acutely to common environmental stress, and to what extent their long-term function during subsequent development may be altered by environment. The experiments will yield a basic understanding of embryonic physiology in vertebrates which will be important in developing corrective procedures for human defects through a combination of gene therapy and embryonic corrective surgery (envisaged by some as the next surgical frontier). This project will train a new cohort of undergraduate and graduate students in the use of contemporary physiological techniques to address critical questions in developmental physiology. The project will increase international collaboration, and the broadening of professional vistas for trainees through the PI's informal Environmental Genetic and Growth Science (EGGS) network of collaborating scientists from six countries. And finally, a greater love of science in high school and middle school teachers and their students will be fostered. Selected secondary school teachers from Denton will participate in original scientific research at UNT, through the PI's collaborative program with the local school district.