Integration of a retrograde signal during synapse formation by glia-secreted TGF-beta ligand
Department of Neurobiology; Budnik Lab; Freeman Lab; Graduate School of Biomedical Sciences, Neuroscience Program
Synapses; Neuroglia; Transforming Growth Factor beta
Glial cells are crucial regulators of synapse formation, elimination, and plasticity [1, 2]. In vitro studies have begun to identify glial-derived synaptogenic factors , but neuron-glia signaling events during synapse formation in vivo remain poorly defined. The coordinated development of pre- and postsynaptic compartments at the Drosophila neuromuscular junction (NMJ) depends on a muscle-secreted retrograde signal, the TGF-beta/BMP Glass bottom boat (Gbb) [3, 4]. Muscle-derived Gbb activates the TGF-beta receptors Wishful thinking (Wit) and either Saxophone (Sax) or Thick veins (Tkv) in motor neurons [3, 4]. This induces phosphorylation of Mad (P-Mad) in motor neurons, its translocation into the nucleus with a co-Smad, and activation of transcriptional programs controlling presynaptic bouton growth . Here we show that NMJ glia release the TGF-beta ligand Maverick (Mav), which likely activates the muscle activin-type receptor Punt to potently modulate Gbb-dependent retrograde signaling and synaptic growth. Loss of glial Mav results in strikingly reduced P-Mad at NMJs, decreased Gbb transcription in muscle, and in turn reduced muscle-to-motor neuron retrograde TGF-beta/BMP signaling. We propose that by controlling Gbb release from muscle, glial cells fine tune the ability of motor neurons to extend new synaptic boutons in correlation to muscle growth. Our work identifies a novel glia-derived synaptogenic factor by which glia modulate synapse formation in vivo.
DOI of Published Version
Curr Biol. 2012 Oct 9;22(19):1831-8. doi: 10.1016/j.cub.2012.07.063. Link to article on publisher's site
Current biology : CB
Fuentes-Medel, Yuly F.; Ashley, James A.; Barria, Romina; Maloney, Rachel; Freeman, Marc R.; and Budnik, Vivian, "Integration of a retrograde signal during synapse formation by glia-secreted TGF-beta ligand" (2012). Neurobiology Publications and Presentations. 136.