Coordination among multiple receptor tyrosine kinase signals controls Drosophila developmental timing and body size

Xueyang Pan; Michael B. O'Connor

doi:10.1016/j.celrep.2021.109644

Coordination among multiple receptor tyrosine kinase signals controls Drosophila developmental timing and body size

Xueyang Pan, Michael B. O'Connor

Genetics, Cell Biology and Development (CBS)

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

In holometabolous insects, metamorphic timing and body size are controlled by a neuroendocrine axis composed of the ecdysone-producing prothoracic gland (PG) and its presynaptic neurons (PGNs) producing PTTH. Although PTTH/Torso signaling is considered the primary mediator of metamorphic timing, recent studies indicate that other unidentified PGN-derived factors also affect timing. Here, we demonstrate that the receptor tyrosine kinases anaplastic lymphoma kinase (Alk) and PDGF and VEGF receptor-related (Pvr), function in coordination with PTTH/Torso signaling to regulate pupariation timing and body size. Both Alk and Pvr trigger Ras/Erk signaling in the PG to upregulate expression of ecdysone biosynthetic enzymes, while Alk also suppresses autophagy by activating phosphatidylinositol 3-kinase (PI3K)/Akt. The Alk ligand Jelly belly (Jeb) is produced by the PGNs and serves as a second PGN-derived tropic factor, while Pvr activation mainly relies on autocrine signaling by PG-derived Pvf2 and Pvf3. These findings illustrate that a combination of juxtacrine and autocrine signaling regulates metamorphic timing, the defining event of holometabolous development.

Original language	English (US)
Article number	109644
Journal	Cell reports
Volume	36
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2021.109644
State	Published - Aug 31 2021

Bibliographical note

Funding Information:
We thank Dr. Ruth Palmer, Dr. Edan Foley, Dr. Norbert Perrimon, and Dr. Ben-Zion Shilo for fly line and reagent sharing. We thank MaryJane Shimell for preforming the in situ jeb and Pvf2/3 hybridization experiments. We also thank the Vienna Drosophila RNAi Center, the Bloomington Drosophila Stock Center, and the National Institute of Genetics in Japan for fly stocks. This work was supported by grant 1R35GM118029 from NIGMS to M.B.O.

Funding Information:
We thank Dr. Ruth Palmer, Dr. Edan Foley, Dr. Norbert Perrimon, and Dr. Ben-Zion Shilo for fly line and reagent sharing. We thank MaryJane Shimell for preforming the in situ jeb and Pvf2/3 hybridization experiments. We also thank the Vienna Drosophila RNAi Center, the Bloomington Drosophila Stock Center, and the National Institute of Genetics in Japan for fly stocks. This work was supported by grant 1R35GM118029 from NIGMS to M.B.O. Conceptualization, M.B.O. and X.P.; methodology, M.B.O. and X.P.; investigation, X.P. and M.B.O.; writing – original draft, X.P.; writing – review & editing, M.B.O. and X.P.; funding acquisition, M.B.O.; supervision, M.B.O. The authors declare no competing interests. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list.

Publisher Copyright:
© 2021 The Authors

Keywords

Drosophila
Jak/Stat
PDGF and VEGF receptor-related
Upd
anaplastic lymphoma kinase
metamorphosis
prothoracic gland
prothoracicotropic hormone
receptor tyrosine kinase

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural

Publisher link

10.1016/j.celrep.2021.109644

Find It

Find It at U of M Libraries

Cite this

@article{784a285466e84ffcafd6a28a31de9c76,

title = "Coordination among multiple receptor tyrosine kinase signals controls Drosophila developmental timing and body size",

abstract = "In holometabolous insects, metamorphic timing and body size are controlled by a neuroendocrine axis composed of the ecdysone-producing prothoracic gland (PG) and its presynaptic neurons (PGNs) producing PTTH. Although PTTH/Torso signaling is considered the primary mediator of metamorphic timing, recent studies indicate that other unidentified PGN-derived factors also affect timing. Here, we demonstrate that the receptor tyrosine kinases anaplastic lymphoma kinase (Alk) and PDGF and VEGF receptor-related (Pvr), function in coordination with PTTH/Torso signaling to regulate pupariation timing and body size. Both Alk and Pvr trigger Ras/Erk signaling in the PG to upregulate expression of ecdysone biosynthetic enzymes, while Alk also suppresses autophagy by activating phosphatidylinositol 3-kinase (PI3K)/Akt. The Alk ligand Jelly belly (Jeb) is produced by the PGNs and serves as a second PGN-derived tropic factor, while Pvr activation mainly relies on autocrine signaling by PG-derived Pvf2 and Pvf3. These findings illustrate that a combination of juxtacrine and autocrine signaling regulates metamorphic timing, the defining event of holometabolous development.",

keywords = "Drosophila, Jak/Stat, PDGF and VEGF receptor-related, Upd, anaplastic lymphoma kinase, metamorphosis, prothoracic gland, prothoracicotropic hormone, receptor tyrosine kinase",

author = "Xueyang Pan and O'Connor, {Michael B.}",

note = "Funding Information: We thank Dr. Ruth Palmer, Dr. Edan Foley, Dr. Norbert Perrimon, and Dr. Ben-Zion Shilo for fly line and reagent sharing. We thank MaryJane Shimell for preforming the in situ jeb and Pvf2/3 hybridization experiments. We also thank the Vienna Drosophila RNAi Center, the Bloomington Drosophila Stock Center, and the National Institute of Genetics in Japan for fly stocks. This work was supported by grant 1R35GM118029 from NIGMS to M.B.O. Funding Information: We thank Dr. Ruth Palmer, Dr. Edan Foley, Dr. Norbert Perrimon, and Dr. Ben-Zion Shilo for fly line and reagent sharing. We thank MaryJane Shimell for preforming the in situ jeb and Pvf2/3 hybridization experiments. We also thank the Vienna Drosophila RNAi Center, the Bloomington Drosophila Stock Center, and the National Institute of Genetics in Japan for fly stocks. This work was supported by grant 1R35GM118029 from NIGMS to M.B.O. Conceptualization, M.B.O. and X.P.; methodology, M.B.O. and X.P.; investigation, X.P. and M.B.O.; writing – original draft, X.P.; writing – review & editing, M.B.O. and X.P.; funding acquisition, M.B.O.; supervision, M.B.O. The authors declare no competing interests. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list. Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = aug,

day = "31",

doi = "10.1016/j.celrep.2021.109644",

language = "English (US)",

volume = "36",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "9",

}

TY - JOUR

T1 - Coordination among multiple receptor tyrosine kinase signals controls Drosophila developmental timing and body size

AU - Pan, Xueyang

AU - O'Connor, Michael B.

N1 - Funding Information: We thank Dr. Ruth Palmer, Dr. Edan Foley, Dr. Norbert Perrimon, and Dr. Ben-Zion Shilo for fly line and reagent sharing. We thank MaryJane Shimell for preforming the in situ jeb and Pvf2/3 hybridization experiments. We also thank the Vienna Drosophila RNAi Center, the Bloomington Drosophila Stock Center, and the National Institute of Genetics in Japan for fly stocks. This work was supported by grant 1R35GM118029 from NIGMS to M.B.O. Funding Information: We thank Dr. Ruth Palmer, Dr. Edan Foley, Dr. Norbert Perrimon, and Dr. Ben-Zion Shilo for fly line and reagent sharing. We thank MaryJane Shimell for preforming the in situ jeb and Pvf2/3 hybridization experiments. We also thank the Vienna Drosophila RNAi Center, the Bloomington Drosophila Stock Center, and the National Institute of Genetics in Japan for fly stocks. This work was supported by grant 1R35GM118029 from NIGMS to M.B.O. Conceptualization, M.B.O. and X.P.; methodology, M.B.O. and X.P.; investigation, X.P. and M.B.O.; writing – original draft, X.P.; writing – review & editing, M.B.O. and X.P.; funding acquisition, M.B.O.; supervision, M.B.O. The authors declare no competing interests. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list. Publisher Copyright: © 2021 The Authors

PY - 2021/8/31

Y1 - 2021/8/31

N2 - In holometabolous insects, metamorphic timing and body size are controlled by a neuroendocrine axis composed of the ecdysone-producing prothoracic gland (PG) and its presynaptic neurons (PGNs) producing PTTH. Although PTTH/Torso signaling is considered the primary mediator of metamorphic timing, recent studies indicate that other unidentified PGN-derived factors also affect timing. Here, we demonstrate that the receptor tyrosine kinases anaplastic lymphoma kinase (Alk) and PDGF and VEGF receptor-related (Pvr), function in coordination with PTTH/Torso signaling to regulate pupariation timing and body size. Both Alk and Pvr trigger Ras/Erk signaling in the PG to upregulate expression of ecdysone biosynthetic enzymes, while Alk also suppresses autophagy by activating phosphatidylinositol 3-kinase (PI3K)/Akt. The Alk ligand Jelly belly (Jeb) is produced by the PGNs and serves as a second PGN-derived tropic factor, while Pvr activation mainly relies on autocrine signaling by PG-derived Pvf2 and Pvf3. These findings illustrate that a combination of juxtacrine and autocrine signaling regulates metamorphic timing, the defining event of holometabolous development.

AB - In holometabolous insects, metamorphic timing and body size are controlled by a neuroendocrine axis composed of the ecdysone-producing prothoracic gland (PG) and its presynaptic neurons (PGNs) producing PTTH. Although PTTH/Torso signaling is considered the primary mediator of metamorphic timing, recent studies indicate that other unidentified PGN-derived factors also affect timing. Here, we demonstrate that the receptor tyrosine kinases anaplastic lymphoma kinase (Alk) and PDGF and VEGF receptor-related (Pvr), function in coordination with PTTH/Torso signaling to regulate pupariation timing and body size. Both Alk and Pvr trigger Ras/Erk signaling in the PG to upregulate expression of ecdysone biosynthetic enzymes, while Alk also suppresses autophagy by activating phosphatidylinositol 3-kinase (PI3K)/Akt. The Alk ligand Jelly belly (Jeb) is produced by the PGNs and serves as a second PGN-derived tropic factor, while Pvr activation mainly relies on autocrine signaling by PG-derived Pvf2 and Pvf3. These findings illustrate that a combination of juxtacrine and autocrine signaling regulates metamorphic timing, the defining event of holometabolous development.

KW - Drosophila

KW - Jak/Stat

KW - PDGF and VEGF receptor-related

KW - Upd

KW - anaplastic lymphoma kinase

KW - metamorphosis

KW - prothoracic gland

KW - prothoracicotropic hormone

KW - receptor tyrosine kinase

UR - http://www.scopus.com/inward/record.url?scp=85114053701&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85114053701&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2021.109644

DO - 10.1016/j.celrep.2021.109644

M3 - Article

C2 - 34469735

AN - SCOPUS:85114053701

SN - 2211-1247

VL - 36

JO - Cell Reports

JF - Cell Reports

IS - 9

M1 - 109644

ER -

Coordination among multiple receptor tyrosine kinase signals controls Drosophila developmental timing and body size

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

Publisher link

Find It

Other files and links

Fingerprint

Cite this