Meeting Abstract
S5.1 Monday, Jan. 5 Cell-Cell Signaling Drives the Evolution of Complex Traits: Introduction- Lung Evo-Devo TORDAY, John/S*; REHAN, Virender/K; Harbor-UCLA Medical Center; Harbor-UCLA Medical Center jtorday@labiomed.org
Physiology is biologic assimilation with the environment through multi-level cell-cell communications. We deconvoluted (Torday and Rehan 2004) lung evolution through Gene Regulatory Networks (GRNs) mediating cell-cell interactions for all lung biology-development, homeostasis, regeneration, and aging. This cell-cell communication model predicts other aspects of vertebrate physiology as adaptational responses. For example, the oxygen-induced differentiation of alveolar mesenchymal stem cells into adipocytes was necessary for the evolution of the lung in land dwelling animals adapting to Phanarezoic oxygen (12-35%). Alveolar adipocytes prevent oxygen radical injury (Torday et al 2001), and produce leptin, augmenting pulmonary surfactant to accommodate increasing alveolar surface area, limited by high systemic vascular pressure, which is compensated for by the evolution of the adrenomedullary beta adrenergic receptor mechanism (βAR). Evolution of peripheral adipocytes fostered endothermy, also driven by the βAR, ratcheting up selection pressure for both respiratory oxygenation and metabolic demand. Combined positive selection for the lung, endothermy and βAR generates further positive selection pressure for the heart, which becomes progressively more complex phylogenetically in tandem with the lung. Increasing heart complexity and size impinge on the gut mesoderm to induce the liver, a regulated source of glucose necessary for the evolution of the neocortex. Neocortical control furthers the integration of these physiologic systems. Such a cell-to-tissue-to-organ-to-systems physiology evolutionary integration through cross-talk between intrinsic and extrinsic factors facilitates the translation of genomics into biology. We will elucidate this evolutionary cell biologic approach, tracing metazoan evolution from sponges to man. Funded by NIH Grants HL055268 (JST) and HL075405 (VKR).
