Metabolic control of progenitor cell propagation during Drosophila tracheal remodeling

Abstract

Adult progenitor cells in the trachea of Drosophila larvae are activated and migrate out of niches when metamorphosis induces tracheal remodeling. Here we show that in response to metabolic deficiency in decaying tracheal branches, signaling by the insulin pathway controls the progenitor cells by regulating Yorkie (Yki)-dependent proliferation and migration. Yki, a transcription coactivator that is regulated by Hippo signaling, promotes transcriptional activation of cell cycle regulators and components of the extracellular matrix in tracheal progenitor cells. These findings reveal that regulation of Yki signaling by the insulin pathway governs proliferation and migration of tracheal progenitor cells, thereby identifying the regulatory mechanism by which metabolic depression drives progenitor cell activation and cell division that underlies tracheal remodeling.

A single-cell atlas of Drosophila trachea reveals glycosylation-mediated Notch signaling in cell fate specification

“…3j and Supplementary Fig. 4d ), which is in fitting with hormonal control of tracheal progenitors by insulin 31 . The cut -expressing subpopulation of PCs was verified by an enhancer trap Gal4 line and an antibody against Cut (Fig.…”

“…To assess the accuracy of clustering, we compared the identified marker genes with results from cell-type-specific transcription profiles. First, a correlation analysis of gene expression showed that the PC cluster displayed the highest similarity with the transcriptomic profile obtained from bulk RNA-seq of progenitor cells 31 (Fig. 1e ).…”

“…3h ). Using a reporter that assays insulin receptor (InR) activity to label the insulin-responsive subpopulation 31 , it was found that the cut -expressing progenitors displayed low levels of InR activity, suggesting the presence of two distinct progenitor subpopulations characterized by either cut expression or InR activity (Fig. 3m-m ”’).…”

“…To further explore the genetic program involved in the diversification of tracheoblasts and understand the function of Notch signaling, we performed RNA-seq of progenitors during their initial process of differentiation. Approximately 10 tracheoblasts from individual progenitor clusters of wandering L3 larvae, white pupae (0 h APF), and 2 h-APF-pupae were dissected 31 . The results of these experiments revealed that the expression level of peb elevated when the differentiation of tracheoblasts commences (Fig.…”

“…In Drosophila , the systemic insulin-like neuropeptides shape the growth of specific tracheal subsets and potentiate tracheal branching 30 . Correspondingly, insulin signaling negatively regulates the migration of tracheal progenitors 31 . Despite these findings, the extent to which dietary conditions modulate tubulogenesis remains vague at the cellular and molecular level.…”