The PHR proteins: intracellular signaling hubs in neuronal development and axon degeneration.

During development, a coordinated and integrated series of events must be accomplished in order to generate functional neural circuits. Axons must navigate toward target cells, build synaptic connections, and terminate outgrowth. The PHR proteins (consisting of mammalian Phr1/MYCBP2, Drosophila Highwire and C.

Netrin and Frazzled regulate presynaptic gap junctions at a Drosophila giant synapse.

Netrin and its receptor, Frazzled, dictate the strength of synaptic connections in the giant fiber system (GFS) of Drosophila melanogaster by regulating gap junction localization in the presynaptic terminal. In Netrin mutant animals, the synaptic coupling between a giant interneuron and the "jump" motor neuron was weakened and dye coupling between these two neurons was severely compromised or absent. In cases in which Netrin mutants displayed apparently normal synaptic anatomy, half of the specimens exhibited physiologically defective synapses and dye coupling between the giant fiber (GF) and the motor neuron was reduced or eliminated, suggesting that gap junctions were disrupted in the Netrin mutants.

Genetic interaction of Neuroglian and Semaphorin1a during guidance and synapse formation.

We have previously demonstrated a function for Neuroglian and Semaphorin1a in Drosophila giant fiber circuit formation. Both molecules are required for guiding the giant fibers out of the brain and have distinct functions during giant synapse formation. In this study we characterized the effects of various combinations of Neuroglian and Semaphorin1a gain and loss of function backgrounds on giant fiber circuitry formation.

A mechanism distinct from highwire for the Drosophila ubiquitin conjugase bendless in synaptic growth and maturation.

The signaling mechanisms that allow the conversion of a growth cone into a mature and stable synapse are yet to be completely understood. Ubiquitination plays key regulatory roles in synaptic development and may be involved in this process. Previous studies identified the Drosophila ubiquitin conjugase bendless (ben) to be important for central synapse formation, but the precise role it plays has not been elucidated.

A conserved role for Drosophila Neuroglian and human L1-CAM in central-synapse formation.

Background: Drosophila Neuroglian (Nrg) and its vertebrate homolog L1-CAM are cell-adhesion molecules (CAM) that have been well studied in early developmental processes. Mutations in the human gene result in a broad spectrum of phenotypes (the CRASH-syndrome) that include devastating neurological disorders such as spasticity and mental retardation. Although the role of L1-CAMs in neurite extension and axon pathfinding has been extensively studied, much less is known about their role in synapse formation.

Bi-directional signaling by Semaphorin 1a during central synapse formation in Drosophila.

Semaphorins have been intensively studied for their role in dendritic and axonal pathfinding, but less is known about their potential role in synapse formation. In the adult giant fiber (GF) system of fruit flies (Drosophila melanogaster), we show that transmembrane Semaphorin 1a (Sema-1a) is involved in synapse formation in addition to its role in guidance during pathfinding. Cell-autonomous rescue experiments showed that Sema-1a is involved in assembly of a central synapse and that it is required both pre- and postsynaptically.

New roles for ubiquitin in the assembly and function of neuronal circuits.

A series of recent papers highlight a prominent role for ubiquitin in the formation and function of neural circuits. These new results focus attention on the molecular remodeling that occurs at various decision points in the life of growth cones and synapses.

Ectopic expression in the giant fiber system of Drosophila reveals distinct roles for roundabout (Robo), Robo2, and Robo3 in dendritic guidance and synaptic connectivity.

The Roundabout (Robo) receptors have been intensively studied for their role in regulating axon guidance in the embryonic nervous system, whereas a role in dendritic guidance has not been explored. In the adult giant fiber system of Drosophila, we have revealed that ectopic Robo expression can regulate the growth and guidance of specific motor neuron dendrites, whereas Robo2 and Robo3 have no effect. We also show that the effect of Robo on dendritic guidance can be suppressed by Commissureless coexpression.