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.
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Animals, Genetically Modified
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Autocrine Communication
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Body Size
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / embryology
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Drosophila melanogaster / enzymology*
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Drosophila melanogaster / genetics
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Ecdysone / metabolism
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Endocrine Glands / embryology
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Endocrine Glands / enzymology*
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ErbB Receptors / genetics
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ErbB Receptors / metabolism
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Extracellular Signal-Regulated MAP Kinases / genetics
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gene Expression Regulation, Developmental
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IMP Dehydrogenase / genetics
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IMP Dehydrogenase / metabolism
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Janus Kinases / genetics
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Janus Kinases / metabolism
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Metamorphosis, Biological*
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Mutation
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / metabolism*
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Receptors, Invertebrate Peptide / genetics
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Receptors, Invertebrate Peptide / metabolism
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STAT Transcription Factors / genetics
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STAT Transcription Factors / metabolism
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Signal Transduction
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Time Factors
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Vascular Endothelial Growth Factors / genetics
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Vascular Endothelial Growth Factors / metabolism
Substances
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Drosophila Proteins
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PVF3 protein, Drosophila
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Pvf2 protein, Drosophila
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Receptors, Invertebrate Peptide
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STAT Transcription Factors
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Transcription Factors
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Vascular Endothelial Growth Factors
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jeb protein, Drosophila
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Ecdysone
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IMP Dehydrogenase
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ras protein, Drosophila
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Egfr protein, Drosophila
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ErbB Receptors
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Pvr protein, Drosophila
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Receptor Protein-Tyrosine Kinases
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tor protein, Drosophila
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Janus Kinases
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hop protein, Drosophila
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Extracellular Signal-Regulated MAP Kinases