TY - JOUR
T1 - The Drosophila Duox maturation factor is a key component of a positive feedback loop that sustains regeneration signaling
AU - Khan, Sumbul Jawed
AU - Abidi, Syeda Nayab Fatima
AU - Skinner, Andrea
AU - Tian, Yuan
AU - Smith-Bolton, Rachel K.
N1 - Funding Information:
This work was funded by a Roy J. Carver Charitable Trust Young Investigator Award (#12-4041) to RKSB, https://www.carvertrust.org, and a National Institutes of Health, National Institute of General Medical Sciences R01 grant (#R01 GM107140) to RKSB, https://www.nigms.nih.gov. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors would like to thank A. Brock, K. Schuster, and L. O?Brien for critical reading of the manuscript and helpful discussions, D. Bohmann, K. Bruckner, A. Stathopoulos, I. Ando, M. Uhlirova, M. Ganfornina, and S. Cohen, the Bloomington Drosophila Stock Center (NIH P40OD018537), the TRiP project at Harvard Medical School (NIH/NIGMS R01-GM084947), the Vienna Drosophila Resource Center, and the Developmental Studies Hybridoma Bank (NICHD, University of Iowa) for reagents. The authors would also like to thank B. Pilas at the Flow Cytometry Facility, A. Hernandez at the High-Throughput Sequencing and Genotyping Unit, and R. Khetani at the High Performance Biological Computing Center, all of which are part of the Roy J. Carver Biotechnology Center at the University of Illinois Urbana-Champaign.
PY - 2017/7
Y1 - 2017/7
N2 - Regenerating tissue must initiate the signaling that drives regenerative growth, and sustain that signaling long enough for regeneration to complete. How these key signals are sustained is unclear. To gain a comprehensive view of the changes in gene expression that occur during regeneration, we performed whole-genome mRNAseq of actively regenerating tissue from damaged Drosophila wing imaginal discs. We used genetic tools to ablate the wing primordium to induce regeneration, and carried out transcriptional profiling of the regeneration blastema by fluorescently labeling and sorting the blastema cells, thus identifying differentially expressed genes. Importantly, by using genetic mutants of several of these differentially expressed genes we have confirmed that they have roles in regeneration. Using this approach, we show that high expression of the gene moladietz (mol), which encodes the Duox-maturation factor NIP, is required during regeneration to produce reactive oxygen species (ROS), which in turn sustain JNK signaling during regeneration. We also show that JNK signaling upregulates mol expression, thereby activating a positive feedback signal that ensures the prolonged JNK activation required for regenerative growth. Thus, by whole-genome transcriptional profiling of regenerating tissue we have identified a positive feedback loop that regulates the extent of regenerative growth.
AB - Regenerating tissue must initiate the signaling that drives regenerative growth, and sustain that signaling long enough for regeneration to complete. How these key signals are sustained is unclear. To gain a comprehensive view of the changes in gene expression that occur during regeneration, we performed whole-genome mRNAseq of actively regenerating tissue from damaged Drosophila wing imaginal discs. We used genetic tools to ablate the wing primordium to induce regeneration, and carried out transcriptional profiling of the regeneration blastema by fluorescently labeling and sorting the blastema cells, thus identifying differentially expressed genes. Importantly, by using genetic mutants of several of these differentially expressed genes we have confirmed that they have roles in regeneration. Using this approach, we show that high expression of the gene moladietz (mol), which encodes the Duox-maturation factor NIP, is required during regeneration to produce reactive oxygen species (ROS), which in turn sustain JNK signaling during regeneration. We also show that JNK signaling upregulates mol expression, thereby activating a positive feedback signal that ensures the prolonged JNK activation required for regenerative growth. Thus, by whole-genome transcriptional profiling of regenerating tissue we have identified a positive feedback loop that regulates the extent of regenerative growth.
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U2 - 10.1371/journal.pgen.1006937
DO - 10.1371/journal.pgen.1006937
M3 - Article
C2 - 28753614
AN - SCOPUS:85026626630
VL - 13
JO - PLoS Genetics
JF - PLoS Genetics
SN - 1553-7390
IS - 7
M1 - e1006937
ER -