A major research focus of stem cell biology is in the understanding of the initial selection and later maintenance of multipotent cells during development and homeostasis. The Drosophila airways offer a unique system for the elucidation of the regional specification of stem cell selection within a complex branched tissue. The fly airway tree is roughly subdivided into 2 types of cells with distinct developmental potentials: A proximally located group of multipotent adult precursor cells (P-fate) and a distally located population of more differentiated cells (D-fate). We show that the GATA-family transcription factor (TF) Grain promotes the P-fate and the POU-homeobox TF Ventral veinless (Vvl/Drifter/U-turned) stimulates the D-fate. Hedgehog and receptor tyrosine kinase (RTK) signaling cooperate with Vvl to drive the D-fate at the expense of the P-fate while negative regulators of either of these signaling pathways ensure P-fate specification. Local concentrations of Decapentaplegic/BMP, Wingless/Wnt and Hedgehog signals differentially regulate the expression of D-factors and P-factors to transform an equipotent primordial field into a concentric pattern of radially different morphogenetic potentials, which gradually gives rise to the distal-proximal organization of distinct cell types in the mature airway. The identification of a genetic mechanism for P- and D-fate selection in flies may aid future studies aiming to identify the mechanisms that spatially confine multipotent cell selection in the embryonic vertebrate lung.


Multipotent versus differentiated cell fate selection in the developing Drosophila airways

Matsuda, R., Hosono, C., Samakovlis, C., Saigo, K.

eLIFE, Dec. 2, 2015