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Fly motor neurons receive and integrate multiple BMP signaling pathways. (A) Diagram of various BMP pathways signaling to fly motor neurons. At synaptic terminals, Gbb/ <t>BMP7</t> binding to BMP receptors on the motor neuron membrane triggers canonical and non-canonical BMP signaling. Gbb is secreted from both muscle (retrograde signaling—marked here “R”) and motor neurons (autocrine signaling—labeled “A”). During canonical BMP signaling, the high-order BMP/BMPR (Gbb/Wit/Tkv/Sax) complexes are endocytosed and transported to the motor neuron soma where they phosphorylate Mad to regulate various transcriptional programs required for NMJ growth and function. During non-canonical signaling, Wit, the BMPRII, signals through LIMK1 to regulate synapse stability. This pathway does not involve Mad or Medea. In addition, the BMPRs Wit, Tkv and Sax, but not Gbb, enable the synaptic/local BMP signaling. (B) Dissection of a third instar larva along the dorsal side exposes the highly stereotyped body wall muscles labeled with phalloidin (blue) and imaged by confocal microscopy. The anti-horseradish peroxidase antibodies (HRP, magenta) label neuronal membranes. Bruchpilot (Brp, red) is a synaptic scaffold which marks the active zones. In response to canonical BMP signaling, pMad (green) accumulates in the motor neuron nuclei within the ventral nerve cord (VNC), the fly equivalent of mammalian spinal cord. In addition, pMad also accumulates in motor neuron synaptic terminals (right upper panels—muscle 6/7 NMJ). Synaptic/junctional pMad forms discrete puncta that co-localize with the active zone scaffold, Brp. Scale bars: 100 μm (larval fillet), 10 μm (others).
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Fly motor neurons receive and integrate multiple BMP signaling pathways. (A) Diagram of various BMP pathways signaling to fly motor neurons. At synaptic terminals, Gbb/ BMP7 binding to BMP receptors on the motor neuron membrane triggers canonical and non-canonical BMP signaling. Gbb is secreted from both muscle (retrograde signaling—marked here “R”) and motor neurons (autocrine signaling—labeled “A”). During canonical BMP signaling, the high-order BMP/BMPR (Gbb/Wit/Tkv/Sax) complexes are endocytosed and transported to the motor neuron soma where they phosphorylate Mad to regulate various transcriptional programs required for NMJ growth and function. During non-canonical signaling, Wit, the BMPRII, signals through LIMK1 to regulate synapse stability. This pathway does not involve Mad or Medea. In addition, the BMPRs Wit, Tkv and Sax, but not Gbb, enable the synaptic/local BMP signaling. (B) Dissection of a third instar larva along the dorsal side exposes the highly stereotyped body wall muscles labeled with phalloidin (blue) and imaged by confocal microscopy. The anti-horseradish peroxidase antibodies (HRP, magenta) label neuronal membranes. Bruchpilot (Brp, red) is a synaptic scaffold which marks the active zones. In response to canonical BMP signaling, pMad (green) accumulates in the motor neuron nuclei within the ventral nerve cord (VNC), the fly equivalent of mammalian spinal cord. In addition, pMad also accumulates in motor neuron synaptic terminals (right upper panels—muscle 6/7 NMJ). Synaptic/junctional pMad forms discrete puncta that co-localize with the active zone scaffold, Brp. Scale bars: 100 μm (larval fillet), 10 μm (others).

Journal: Current topics in developmental biology

Article Title: Local BMP signaling: A sensor for synaptic activity that balances synapse growth and function

doi: 10.1016/bs.ctdb.2022.04.001

Figure Lengend Snippet: Fly motor neurons receive and integrate multiple BMP signaling pathways. (A) Diagram of various BMP pathways signaling to fly motor neurons. At synaptic terminals, Gbb/ BMP7 binding to BMP receptors on the motor neuron membrane triggers canonical and non-canonical BMP signaling. Gbb is secreted from both muscle (retrograde signaling—marked here “R”) and motor neurons (autocrine signaling—labeled “A”). During canonical BMP signaling, the high-order BMP/BMPR (Gbb/Wit/Tkv/Sax) complexes are endocytosed and transported to the motor neuron soma where they phosphorylate Mad to regulate various transcriptional programs required for NMJ growth and function. During non-canonical signaling, Wit, the BMPRII, signals through LIMK1 to regulate synapse stability. This pathway does not involve Mad or Medea. In addition, the BMPRs Wit, Tkv and Sax, but not Gbb, enable the synaptic/local BMP signaling. (B) Dissection of a third instar larva along the dorsal side exposes the highly stereotyped body wall muscles labeled with phalloidin (blue) and imaged by confocal microscopy. The anti-horseradish peroxidase antibodies (HRP, magenta) label neuronal membranes. Bruchpilot (Brp, red) is a synaptic scaffold which marks the active zones. In response to canonical BMP signaling, pMad (green) accumulates in the motor neuron nuclei within the ventral nerve cord (VNC), the fly equivalent of mammalian spinal cord. In addition, pMad also accumulates in motor neuron synaptic terminals (right upper panels—muscle 6/7 NMJ). Synaptic/junctional pMad forms discrete puncta that co-localize with the active zone scaffold, Brp. Scale bars: 100 μm (larval fillet), 10 μm (others).

Article Snippet: These signaling pathways are triggered by the BMP7 homolog, Glass bottom boat (Gbb), secreted from the muscle (retrograde signaling) ( McCabe et al., 2003 ) or from the motor neurons (autocrine signaling) ( James et al., 2014 ) and require two type-I BMP receptors (BMPRI), Tkv and Sax, one type-II BMP receptor, Wit, and the downstream effectors Mad and Medea ( Aberle et al., 2002 ; Marques et al., 2003 ; McCabe et al., 2004 , 2003 ; Rawson, Lee, Kennedy, & Selleck, 2003 ).

Techniques: Protein-Protein interactions, Binding Assay, Membrane, Labeling, Dissection, Muscles, Confocal Microscopy