Biology subjects

Uttekar, B.

Publications and source records attributed to Uttekar, B..

3 recordsLinked to original sources

bioRxiv2025

Recognition of pathogenic bacteria by intestinal progenitors promotes adult Drosophila midgut regeneration via PGRP-MKK3-p38 signalling.

When enteropathogenic bacteria breach the intestinal epithelium, they are recognized by epithelial and immune cells that elicit an intestinal regenerative response. However, less is known about whether and how intestinal progenitors directly detect invading pathogenic bacteria and couple this to their proliferation. Here we show that adult Drosophila midgut progenitors recognise peptidoglycan from pathogenic bacteria through the peptidoglycan recognition proteins, PGRP-LC and PGRP-LE, and translate this to ISC proliferation by stimulating MKK3-p38 signalling. Moreover, we find that PGRP-LC/LE-MKK3-p38 signalling in progenitors regulates p38 activation throughout the midgut epithelium after infection, indicating that progenitors can influence the regenerative niche in a non-cell autonomous manner. Whilst it was previously thought that ISC proliferation in both mammals and flies is driven solely by damage-induced signals after infection, our work reveals that progenitors can directly recognise pathogenic bacteria and mount a strong parallel regenerative response that spreads throughout the midgut epithelium. Increased ISC proliferation after bacterial recognition may also serve as a strategy to repopulate the epithelium with uninfected cells.

developmental biology↗

bioRxiv2023

Mitochondrial morphology dynamics and ROS regulate apical polarity and differentiation in Drosophila follicle cells

Mitochondrial morphology dynamics regulate signaling pathways during epithelial cell formation and differentiation. The mitochondrial fission protein Drp1 affects the appropriate activation of EGFR and Notch signaling-driven differentiation of posterior follicle cells in Drosophila oogenesis. The mechanisms by which Drp1 regulates epithelial polarity during differentiation are not known. In this study, we show that Drp1 depleted follicle cells are constricted in early stages and present in multiple layers at later stages with decreased levels of apical polarity protein aPKC. This defect is suppressed by additional depletion of mitochondrial fusion protein Opa1. Opa1 depletion leads to mitochondrial fragmentation and increased reactive oxygen species (ROS) in follicle cells. We find that increasing ROS by depleting the ROS scavengers, mitochondrial SOD2, and catalase also leads to mitochondrial fragmentation. Further, the loss of Opa1, SOD2, and catalase partially restores the defects in epithelial polarity and aPKC along with EGFR and Notch signaling in Drp1 depleted follicle cells. Our results show a crucial interaction between mitochondrial morphology, ROS generation, and epithelial cell polarity formation during the differentiation of follicle epithelial cells in Drosophila oogenesis. Summary statementMitochondrial fission protein Drp1 regulates epithelial follicle cell differentiation in Drosophila oogenesis. Increasing ROS and mitochondrial fragmentation suppresses the defects in epithelial polarity, and differentiation in Drp1 depleted follicle cells.

developmental biology↗

bioRxiv2021

Mitochondrial fusion regulates proliferation and differentiation in the type II neuroblast lineage in Drosophila

Optimal mitochondrial function determined by mitochondrial dynamics, morphology and activity is coupled to stem cell differentiation and organism development. However, the mechanisms of interaction of signaling pathways with mitochondrial morphology and activity are not completely understood. We assessed the role of mitochondrial fusion and fission in differentiation of neural stem cells called neuroblasts (NB) in the Drosophila brain. Depletion of mitochondrial inner membrane fusion protein Opa1 and mitochondrial outer membrane protein Marf in the Drosophila type II neuroblast lineage led to mitochondrial fragmentation and loss of activity. Opa1 and Marf depletion did not affect the numbers and polarity of type II neuroblasts but led to a decrease in proliferation and differentiation of cells in the lineage. On the contrary, loss of mitochondrial fission protein Drp1 led to mitochondrial fusion but did not show defects in proliferation and differentiation. Depletion of Drp1 along with Opa1 or Marf also led to mitochondrial fusion and suppressed fragmentation, loss of mitochondrial activity, proliferation and differentiation in the type II NB lineage. We found that Notch signaling depletion via the canonical pathway showed mitochondrial fragmentation and loss of differentiation similar to Opa1 mutants. An increase in Notch signaling required mitochondrial fusion for NB proliferation. Further, Drp1 mutants in combination with Notch depletion showed mitochondrial fusion and drove differentiation in the lineage suggesting that fused mitochondria can influence Notch signaling driven differentiation in the type II NB lineage. Our results implicate a crosstalk between Notch signalling, mitochondrial activity and mitochondrial fusion as an essential step in type II NB differentiation.

developmental biology↗