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Molecular Determinants of Lung Development
The National Heart, Lung, and Blood Institute (NHLBI) supports a strong portfolio of fundamental research on the determinants of lung development, which is contributing new information on the multiple key genes, molecules and signaling pathways that underlie the developmental process.
The Division of Lung Diseases (DLD) of NHLBI convened a workshop on September 7-8, 2011 to identify key knowledge gaps and priority areas in lung development research and to make recommendations for future research directions. This workshop sought to facilitate communications among diverse research groups, including scientists outside of the lung field, to encourage novel and systematic approaches to solving fundamental questions and to identify opportunities for advancing lung development research. Prior to the workshop, four working groups were organized to identify critical topics in multiple scientific areas. At the workshop, group leaders presented the consensus of views they compiled and facilitated the discussion of questions related to topics considered to be of high priority:
Environmental Impacts on Early Lung Development: This session focused on issues surrounding appropriate tissue samples to assess the impact of environmental insults on lung development and accessibility of these samples; generational and trans-generational conditions that are predictive of pulmonary disease; interactions between the macroenvironment and the pulmonary microenvironment; identity and role of fetal-derived lung factors that may be involved in signaling for parturition; and mechanisms through which the environment interacts with genes and chromatin that predispose the fetus to postnatal pulmonary disease.
Early Cell Fate and Morphogenesis: This panel raised a number of seminal topics, including: identifying temporal/spatial conditions that enable proper reactivation/inhibition of developmental pathways to promote lung repair and regeneration; employing developing lung to explore mechanisms and therapeutic options for lung repair and regeneration; the role of developmental pathways in lineage specification and differentiation; effects of epigenetic mechanisms on lung development and regeneration; role of defects in early morphological processes in influencing susceptibility to lung disease; identifying determinants of lung maturation events such as sacculation and alveologenesis; regulation of lung size and transition from growth to maturation; and coordination of heart and lung development.
Mechanisms of Lung Cell Differentiation: The issues discussed in this session included: the influence of cellular architecture in tissue morphogenesis and cell fate during lung differentiation and disease; the role of mechanotransduction in lung epithelial differentiation; functions of primary cilia in the airway epithelium and their relationship to motile ciliogenesis; role of cellular niche and extracellular matrix in regulating lung epithelial cell fate; epithelial-mesenchymal interactions in regulating cell differentiation; developmental basis of lung metaplasia in injury; role of protein degradation in lung development; and links between cellular phenotype and lung physiology.
Tissue Interactions in Lung Development: Topics of discussion included: genetic and epigenetic factors regulating and coordinating patterning of airways with that of lung blood vessels, lymphatics and neuronal innervations; identity and role of the relevant signaling pathways that govern tissue interactions; major factors impacting on these pathways, such as oxygenation, metabolic events, immune and inflammatory systems, endogenous progenitor cells, the microbiome, and mechanical factors related to the heart, blood vessels, musculoskeletal system, pleura, and placenta; development of pulmonary veins at the intersection of the heart and lung; development and function of lung lymphatics and their influence on lung maturation and function; roles of nerves in lung airway, vascular, and lymphatic development; pleural biology and potential functions of the pleura in developmental signaling and structural organization of the embryonic lung.
NIH CSR Staff
Last Updated: December 2011