We seek to answer questions at the interface between morphogenesis and differentiation in the lung.
- Branching morphogenesis does not continue forever; what mechanism stops branching and how such a mechanism is coordinated with gestation time to ensure a functional lung at birth? Whether and how does premature birth interfere with this mechanism?
- What sets the boundary between the two airway compartments, the proximal conducting airways and distal alveolar regions? Does it involve a morphogen gradient as demonstrated in the classic studies of embryonic patterning in Drosophila?
- What controls the tapering in tube diameter over branch generation such that the airway tree achieves optimal transport efficiency as defined by Murray's Law, which states that the cube of the parent tube diameter is equal to the sum of the cubes of its two daughter tube diameters? Whether and how does tube diameter regulate the number and distribution of differentiated airway cells?
We utilize a three-dimensional imaging technology, optical projection tomography, to simultaneously visualize morphogenesis and differentiation in the whole lung. In combination with mouse genetics and genomic approaches, we have identified key transcriptional and hormonal regulators that will allow us to address each of these questions. Interested individuals can contact firstname.lastname@example.org for details.