Poster P6 - Coupling mitochondrial energy metabolism to the mechanics of tissue morphogenesis in the developing avian lung

Introduction: Energy at a molecular scale is required to fuel the cellular behaviors that give rise to tissue shape. Despite a deep understanding of cellular energy metabolism, it is unclear whether energy metabolism is patterned during tissue morphogenesis in a way that correlates with and/or drives gene expression or mechanical forces. We have measured the spatial patterns of energy metabolism, primarily through the lens of mitochondrial activity, in the early embryonic chicken lung. At this stage of development, the chicken lung consists of tubes of simple columnar epithelium surrounded by a loose mesenchyme. To generate the first several branches off the dorsal surface of the primary bronchus, subsets of epithelial cells undergo actomyosin-driven apical constriction. The first three of these branching events are highly stereotyped in time and location; we therefore focused on this geometrically ideal system to study how energy metabolism relates to the patterns of mechanical force that drive changes in tissue morphology.

Materials and

Methods: We isolated embryonic chicken lungs and used immunofluorescence analysis for TOM20 to measure mitochondrial density. Additionally, we cultured lung explants in the presence of the fluorescent dyes MitoView633 and ATPRed1 to measure mitochondrial membrane potential. We also imaged and quantified these parameters in lung explants treated with oligomycin, blebbistatin, or aphidicolin to parse the effects of respiration, actomyosin contractility, and proliferation on mitochondrial energy metabolism and lung morphogenesis. Finally, we measured oxygen consumption rates to quantify the energy budget of this developing organ.

Results, Conclusions, and Discussions: We found that mitochondrial density and membrane potential are increased within the epithelium at sites of branch initiation in the developing lung. Additionally, the branching epithelium has a higher oxygen consumption rate than nearby non-branching epithelium. Furthermore, inhibiting mitochondrial respiration prevents further branch initiation but surprisingly does not affect tissue growth. These data reveal that mitochondrial energy metabolism is patterned concurrently with apical constriction and branching morphogenesis in the lung. These findings offer a novel perspective on how patterns of energy metabolism are intricately linked to the mechanical forces that drive tissue morphogenesis. This study paves the way for deeper insights into the fundamental principles guiding tissue and organ development.

Acknowledgements (Optional): This research is supported by an NIH Director’s Pioneer Award (HD111539), and the NSF Postdoctoral Research Fellowships in Biology Program (Grant No. 2305831).