The elaborately branched structures of some organs—lungs, kidneys, mammary glands, blood vessels—are necessary for proper function. Premature babies, with underdeveloped lungs and kidneys, can suffer lifelong complications such as respiratory disease or diabetes.
A better understanding of the mechanisms that govern branching morphogenesis is desperately needed.
Our past research has focused on LIN28, an RNA-binding protein and its interactions with the microRNA let-7. We previously discovered that the LIN28/Let-7 axis regulates the developmental timing of branching morphogenesis via both miRNA-dependent and miRNA-independent mechanisms.
Recently, we discovered LIN28A binds Sox2 and Sox9 mRNAs to regulate their stability and resulting protein expression, revealing a LIN28/let-7/SOX2/SOX9 feedback circuit.
Still there is much unknown about how and when the switch from mRNA-dependance to miRNA-dependance occurs in the lung and whether this occurs in the kidney and other branching organs such as the mammary gland and vasculature.
Our goals are to dissect these potential mechanisms of post-transcriptional mRNA control and understand how these phenotypes differ from previously described effects on proliferation and cell death.