Morphogens and synaptogenesis in Drosophila

Abstract

During development and adult life synapses are remodeled in response to genetic programs and environmental cues. This synaptic plasticity is thought to be the basis of learning and memory. The larval neuromuscular junction of Drosophila is established during embryogenesis and grows during larval development to accommodate muscle growth and maintain synaptic homeostasis. This growth is dependent on bidirectional communication between the motoneuron and the muscle fiber. The best-characterized retrograde signaling pathway is defined by Glass bottom boat (Gbb), a morphogen of the transforming growth factor-beta (TGF-beta) superfamily. Gbb acts as a muscle-derived retrograde signal that activates the TGF-beta pathway presynaptically. This pathway includes the type II receptor Wishful thinking, type I receptors Thick veins and Saxophone, and the second messenger Smads Mothers against dpp (Mad) and Medea. Mutations that block this pathway result in small synapses that are morphologically aberrant and severely impaired functionally. An emerging anterograde signaling pathway is defined by Wingless, a morphogen of the Wnt family that acts as a motoneuron-derived anterograde signal required for both pre- and postsynaptic development. In the absence of Wingless the neuronal microtubule cytoskeleton regulator Futsch is down-regulated and synaptic growth impaired. Some of these morphogens have conserved roles in mammalian synaptogenesis, and genetic analysis suggests that additional signaling molecules are required for synaptic growth at the Drosophila neuromuscular junction.

Genetic Modifiers of Drosophila Palmitoyl–Protein Thioesterase 1-Induced Degeneration

“…These functions of endocytic trafficking are on display in all cell types, including neurons where it controls the development and activity-dependent modulation of synapses. The identification of the TGF-b type I receptor sax as a suppressor in our screen suggests a connection between Ppt1 function and a pathway whose modulation by endocytosis is critical for the development and maintenance of the neuromuscular junction in Drosophila (Sweeney and Davis 2002;Dermaut et al 2005;Marques 2005).…”

“…EY(2)4377-driven expression of sax was confirmed using a UAS:sax transgene (Table 1; data not shown). TGF-b signaling is known to play a role in multiple processes during Drosophila development, including the formation of the neuromuscular junction (Marques 2005).…”

Cell Type-Specific Requirements for Heparan Sulfate Biosynthesis at the Drosophila Neuromuscular Junction: Effects on Synapse Function, Membrane Trafficking, and Mitochondrial Localization

“…Although we cannot rule out rescue by the very low level of elav-Gal4-driven expression in muscle cells, neuronal HS synthesis appears to be critical for muscle integrity. These results may reflect the need for HS molecules on the surface of one synaptic partner modulating activities in the other cell (Marqués, 2005).…”

Plasticity and Second Messengers During Synapse Development

“…Glass bottom boat/BMPs-The product of the glass bottom boat (gbb) gene is a member of the BMP subfamily of the TGF-b superfamily of morphogens, and at the NMJ is secreted by muscle cells to promote presynaptic growth and to regulate neurotransmitter release (Marques, 2005). The signal transduction pathway activated by Gbb release from the muscles is thought to provide a retrograde signal to motorneurons, thus coupling muscle growth to changes in strength of the presynaptic input to maintain synaptic strength.…”