TY - JOUR
T1 - Pvr and distinct downstream signaling factors are required for hemocyte spreading and epidermal wound closure at Drosophila larval wound sites
AU - Tsai, Chang Ru
AU - Wang, Yan
AU - Jacobson, Alec
AU - Sankoorikkal, Niki
AU - Chirinos, Josue D.
AU - Burra, Sirisha
AU - Makthal, Nishanth
AU - Kumaraswami, Muthiah
AU - Galko, Michael J.
N1 - Funding Information:
Work in the Galko lab was supported through a “people not projects” mechanism: R35GM126929 of the National Institute of General Medical Sciences (NIGMS). C.-R.T. was supported by an American Heart Association (AHA) predoctoral fellowship (16PRE30880004). A.J., N.S., and J.D.C. were supported by the Cancer Prevention and Research Institute of Texas (CPRIT) CURE Summer Undergraduate Research Training Program at MD Anderson Cancer Center (RP170067).
Publisher Copyright:
© The Author(s) 2021.
PY - 2022/1
Y1 - 2022/1
N2 - Tissue injury is typically accompanied by inflammation. In Drosophila melanogaster larvae, wound-induced inflammation involves adhesive capture of hemocytes at the wound surface followed by hemocyte spreading to assume a flat, lamellar morphology. The factors that mediate this cell spreading at the wound site are not known. Here, we discover a role for the platelet-derived growth factor/vascular endothelial growth factor-related receptor (Pvr) and its ligand, Pvf1, in blood cell spreading at the wound site. Pvr and Pvf1 are required for spreading in vivo and in an in vitro spreading assay where spreading can be directly induced by Pvf1 application or by constitutive Pvr activation. In an effort to identify factors that act downstream of Pvr, we performed a genetic screen in which select candidates were tested to determine if they could suppress the lethality of Pvr overexpression in the larval epidermis. Some of the suppressors identified are required for epidermal wound closure (WC), another Pvr-mediated wound response, some are required for hemocyte spreading in vitro, and some are required for both. One of the downstream factors, Mask, is also required for efficient wound-induced hemocyte spreading in vivo. Our data reveal that Pvr signaling is required for wound responses in hemocytes (cell spreading) and defines distinct downstream signaling factors that are required for either epidermal WC or hemocyte spreading.
AB - Tissue injury is typically accompanied by inflammation. In Drosophila melanogaster larvae, wound-induced inflammation involves adhesive capture of hemocytes at the wound surface followed by hemocyte spreading to assume a flat, lamellar morphology. The factors that mediate this cell spreading at the wound site are not known. Here, we discover a role for the platelet-derived growth factor/vascular endothelial growth factor-related receptor (Pvr) and its ligand, Pvf1, in blood cell spreading at the wound site. Pvr and Pvf1 are required for spreading in vivo and in an in vitro spreading assay where spreading can be directly induced by Pvf1 application or by constitutive Pvr activation. In an effort to identify factors that act downstream of Pvr, we performed a genetic screen in which select candidates were tested to determine if they could suppress the lethality of Pvr overexpression in the larval epidermis. Some of the suppressors identified are required for epidermal wound closure (WC), another Pvr-mediated wound response, some are required for hemocyte spreading in vitro, and some are required for both. One of the downstream factors, Mask, is also required for efficient wound-induced hemocyte spreading in vivo. Our data reveal that Pvr signaling is required for wound responses in hemocytes (cell spreading) and defines distinct downstream signaling factors that are required for either epidermal WC or hemocyte spreading.
KW - Cell-spreading
KW - Drosophila
KW - Hemocytes
KW - Inflammation
KW - Larvae
KW - Pvr
KW - Wound closure
KW - Vascular Endothelial Growth Factor A
KW - Drosophila Proteins/genetics
KW - Epidermis
KW - Receptor Protein-Tyrosine Kinases
KW - Drosophila melanogaster/genetics
KW - Larva/genetics
KW - Animals
KW - Egg Proteins/physiology
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U2 - 10.1093/G3JOURNAL/JKAB388
DO - 10.1093/G3JOURNAL/JKAB388
M3 - Article
C2 - 34751396
AN - SCOPUS:85123572973
SN - 2160-1836
VL - 12
JO - G3: Genes, Genomes, Genetics
JF - G3: Genes, Genomes, Genetics
IS - 1
M1 - jkab388
ER -