The BMP homolog Gbb provides a retrograde signal that regulates synaptic growth at the Drosophila neuromuscular junction

Brian D. McCabe, Guillermo Marqués, A. Pejmun Haghighi, Richard D. Fetter, M. Lisa Crotty, Theodore E. Haerry, Corey S. Goodman, Michael B. O'Connor

Research output: Contribution to journalArticlepeer-review

296 Scopus citations

Abstract

We show that the BMP ortholog Gbb can signal by a retrograde mechanism to regulate synapse growth of the Drosophila neuromuscular junction (NMJ). gbb mutants have a reduced NMJ synapse size, decreased neurotransmitter release, and aberrant presynaptic ultrastructure. These defects are similar to those we observe in mutants of BMP receptors and Smad transcription factors. However, whereas these BMP receptors and signaling components are required in the presynaptic motoneuron, Gbb expression is required in large part in postsynaptic muscles; gbb expression in muscle rescues key aspects of the gbb mutant phenotype. Consistent with this notion, we find that blocking retrograde axonal transport by overexpression of dominant-negative p150/Glued in neurons inhibits BMP signaling in motoneurons. These experiments reveal that a muscle-derived BMP retrograde signal participates in coordinating neuromuscular synapse development and growth.

Original languageEnglish (US)
Pages (from-to)241-254
Number of pages14
JournalNeuron
Volume39
Issue number2
DOIs
StatePublished - Jul 17 2003

Bibliographical note

Funding Information:
We thank Kristy Wharton for generously supplying gbb mutant stocks and UAS- gbb constructs. We are grateful to Grace Panganiban and Peter ten Dijke for sending samples of antibodies. We acknowledge Tom Hays for suggesting the Dynein disruption experiments and we acknowledge Osamu Shimmi for proposing and giving advice in the punt RNAi experiments. We thank the Bloomington Stock center for Drosophila stocks. B.D.M. was supported by a Wellcome Trust Prize Traveling Fellowship. M.B.O. is an associate investigator of the Howard Hughes Medical Institute.

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