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Heterochrony is an enabling concept in evolution theory that metaphorically captures the mechanism of biologic change due to mechanisms of growth and development. The spatio-temporal patterns of morphogenesis are determined by cell-to-cell signaling mediated by specific soluble growth factors and their cognate receptors on nearby cells of different germline origins. Subsequently, down-stream production of second messengers generates patterns of form and function. Environmental upheavals such as Romer's hypothesized drying up of bodies of water globally caused the vertebrate water-land transition. That transition caused physiologic stress, modifying cell-cell signaling to generate terrestrial adaptations of the skeleton, lung, skin, kidney and brain. These tissue-specific remodeling events occurred as a result of the duplication of the Parathyroid Hormone-related Protein Receptor (PTHrPR) gene, expressed in mesodermal fibroblasts in close proximity to ubiquitously expressed endodermal PTHrP, amplifying this signaling pathway. Examples of how and why PTHrPR amplification affected the ontogeny, phylogeny, physiology and pathophysiology of the lung are used to substantiate and further our understanding through insights to the heterochronic mechanisms of evolution, such as the fish swim bladder evolving into the vertebrate lung, interrelated by such functional homologies as surfactant and mechanotransduction. Instead of the conventional description of this phenomenon, lung evolution can now be understood as adaptive changes in the cellular-molecular signaling mechanisms underlying its ontogeny and phylogeny. [ABSTRACT FROM AUTHOR]

Homeostasis is conventionally thought of merely as a synchronic (same time) servo-mechanism that maintains the status quo for organismal physiology. However, when seen from the perspective of developmental physiology, homeostasis is a robust, dynamic, intergenerational, diachronic (across-time) mechanism for the maintenance, perpetuation and modification of physiologic structure and function. The integral relationships generated by cell-cell signaling for the mechanisms of embryogenesis, physiology and repair provide the needed insight to the scale-free universality of the homeostatic principle, offering a novel opportunity for a Systems approach to Biology. Starting with the inception of life itself, with the advent of reproduction during meiosis and mitosis, moving forward both ontogenetically and phylogenetically through the evolutionary steps involved in adaptation to an ever-changing environment, Biology and Evolution Theory need no longer default to teleology. [ABSTRACT FROM AUTHOR]