http://www.jneurosci.org/content/33/45/17937.abstract
Abstract
At the Drosophila
neuromuscular junction (NMJ), the loss of retrograde, trans-synaptic BMP
signaling causes motoneuron terminals to have fewer
synaptic boutons, whereas increased neuronal
activity results in a larger synapse with more boutons. Here, we show
that an
early and transient BMP signal is necessary and
sufficient for NMJ growth as well as for activity-dependent synaptic
plasticity.
This early critical period was revealed by the
temporally controlled suppression of Mad, the SMAD1 transcriptional
regulator.
Similar results were found by genetic rescue
tests involving the BMP4/5/6 ligand Glass bottom boat (Gbb) in muscle,
and alternatively
the type II BMP receptor Wishful Thinking (Wit)
in the motoneuron. These observations support a model where the muscle
signals
back to the innervating motoneuron's nucleus to
activate presynaptic programs necessary for synaptic growth and
activity-dependent
plasticity. Molecular genetic gain- and
loss-of-function studies show that genes involved in NMJ growth and
plasticity, including
the adenylyl cyclase Rutabaga, the Ig-CAM
Fasciclin II, the transcription factor AP-1 (Fos/Jun), and the adhesion
protein
Neurexin, all depend critically on the canonical
BMP pathway for their effects. By contrast, elevated expression of Lar,
a
receptor protein tyrosine phosphatase found to
be necessary for activity-dependent plasticity, rescued the phenotypes
associated
with the loss of Mad signaling. We also find
that synaptic structure and function develop using genetically
separable, BMP-dependent
mechanisms. Although synaptic growth depended on
Lar and the early, transient BMP signal, the maturation of
neurotransmitter
release was independent of Lar and required
later, ongoing BMP signaling.
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