TY - JOUR
T1 - Integration of a retrograde signal during synapse formation by glia-secreted TGF-β ligand
AU - Fuentes-Medel, Yuly
AU - Ashley, James
AU - Barria, Romina
AU - Maloney, Rachel
AU - Freeman, Marc
AU - Budnik, Vivian
N1 - Funding Information:
We thank members of the Freeman and Budnik lab for helpful discussions. We also thank Tzumin Lee for sharing UAS-Mav-RNAi1 flies prior to publication, Mary Logan for sharing UAS-mCD8::mCherry flies, and Kristi Wharton for gbb 1 mutant flies. This work was supported by National Institutes of Health grants R01 MH070000 to V.B. and NS053538 to M.F.
PY - 2012/10/9
Y1 - 2012/10/9
N2 - Glial cells are crucial regulators of synapse formation, elimination, and plasticity [1, 2]. In vitro studies have begun to identify glial-derived synaptogenic factors [1], 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-β/BMP Glass bottom boat (Gbb) [3, 4]. Muscle-derived Gbb activates the TGF-β 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 [5]. Here we show that NMJ glia release the TGF-β 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-β/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.
AB - Glial cells are crucial regulators of synapse formation, elimination, and plasticity [1, 2]. In vitro studies have begun to identify glial-derived synaptogenic factors [1], 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-β/BMP Glass bottom boat (Gbb) [3, 4]. Muscle-derived Gbb activates the TGF-β 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 [5]. Here we show that NMJ glia release the TGF-β 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-β/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.
UR - http://www.scopus.com/inward/record.url?scp=84867401472&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867401472&partnerID=8YFLogxK
U2 - 10.1016/j.cub.2012.07.063
DO - 10.1016/j.cub.2012.07.063
M3 - Article
C2 - 22959350
AN - SCOPUS:84867401472
SN - 0960-9822
VL - 22
SP - 1831
EP - 1838
JO - Current Biology
JF - Current Biology
IS - 19
ER -