Rodney K. Murphey

Florida Atlantic University

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Tanja A. Godenschwege

Florida Atlantic University

Melissa A. Borgen

Florida Institute of Technology

Corey S. Goodman

Stanford University

Smitha Babu Uthaman

Florida Atlantic University

Andrew A. Hill

Auckland City Hospital

Doreen Potter

University at Albany, State University of New York

Aruna Khan

Florida State University

Xiaoliang Shan-Crofts

University of Massachusetts Amherst

Lawrence Bodenstein

Donald & Barbara Zucker School of Medicine at Hofstra/Northwell

Brian O. Orr

University of California, San Francisco

Cooperative Institutions

Florida Atlantic University

University at Albany, State University of New York

Albany State University

University of Massachusetts Amherst

Stanford University

Marine Biological Laboratory

Columbia University

University of Pennsylvania

Howard Hughes Medical Institute

Rutgers, The State University of New Jersey

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Starting Points for a Developmental Genetics of Nerve Patterns

American Zoologist (1982)

R. Kevin Hunt Robert Tompkins Dana C. Reinschmidt Lawrence Bodenstein Rodney K. Murphey

SYNOPSIS. The genie control of the development of neural morphology and specific neural connections is little known, primarily because of a paucity of neurological mutants in animal models suitable for experimental manipulation. However, by using cell markers—such as tetraploidy, a large cell marker whose development is described here—the development of single retinal cells in tetraploid embryos, the growth of marked polyclones in chimeric eyes, and the central connections of various chimeric eyes have been analyzed to identify the strategies used in molding eye morphology and establishing precise central connections. Theoretical models and computer simulations were used to draw inferences about the information used to accomplish the identified strategies. This analysis resulted in predictions about the sorts of mutant genes which might be found to affect neural ontogeny.

Behavioural genetics

10.1093/icb/22.1.185

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Citations (9)

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

Neural Development (2016)

Brock Grill Rodney K. Murphey Melissa A. Borgen

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. elegans RPM-1) function in each of these events in development. Here, we review PHR function across species, as well as the myriad of signaling pathways PHR proteins regulate. These findings collectively suggest that the PHR proteins are intracellular signaling hubs, a concept we explore in depth. Consistent with prominent developmental functions, genetic links have begun to emerge between PHR signaling networks and neurodevelopmental disorders, such as autism, schizophrenia and intellectual disability. Finally, we discuss the recent and important finding that PHR proteins regulate axon degeneration, which has further heightened interest in this fascinating group of molecules.

Neural Development

Biological neural network

10.1186/s13064-016-0063-0

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Citations (57)

Target neuron specification of short-term synaptic facilitation and depression in the cricket CNS

Journal of Neurobiology (1998)

Kathleen A. Killian Rodney K. Murphey

We investigated the role of retrograde signals in the regulation of short-term synaptic depression and facilitation by characterizing the form of plasticity expressed at novel synapses on four giant interneurons in the cricket cercal sensory system. We induced the formation of novel synapses by transplanting a mesothoracic leg and its associated sensory neurons to the cricket terminal abdominal segment. Axons of ectopic leg sensory neurons regenerated and innervated the host terminal abdominal ganglion forming monosynaptic connections with the medial giant interneuron (MGI), lateral giant interneuron (LGI), and interneurons 7-1a and 9-2a. The plasticity expressed by these synapses was characterized by stimulating a sensory neuron with pairs of stimuli at various frequencies or with trains of 10 stimuli delivered at 100 Hz and measuring the change in excitatory postsynaptic potential amplitude recorded in the postsynaptic neuron. Novel synapses of a leg tactile hair on 7-1a depressed, as did control synapses of cercal sensory neurons on this interneuron. Novel synapses of leg campaniform sensilla (CS) sensory neurons on MGI, like MGI's control synapses, always facilitated. The form of plasticity expressed by novel synapses is thus consistent with that observed at control synapses. Leg CS synapses with 9-2a also facilitated; however, the plasticity expressed by these sensory neurons is dependent on the identity of the postsynaptic cell since the synapses these same sensory neurons formed with LGI always depressed. We conclude that the form of plasticity expressed at these synaptic connections is determined retrogradely by the postsynaptic cell. © 1998 John Wiley & Sons, Inc. J Neurobiol 37: 700–714, 1998

Facilitation

Neural facilitation

Depression

10.1002/(sici)1097-4695(199812)37:4<700::aid-neu16>3.0.co;2-h

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Citations (6)

A Mechanism Distinct from Highwire for theDrosophilaUbiquitin Conjugase Bendless in Synaptic Growth and Maturation

Journal of Neuroscience (2008)

Smitha Babu Uthaman Tanja A. Godenschwege Rodney K. Murphey

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. Our studies indicate that Ben plays a pivotal role in synaptic growth and maturation. We have determined that an incipient synapse is present with a high penetrance in ben mutants, suggesting that Ben is required for a developmental step after target recognition. We used cell-autonomous rescue experiments to show that Ben has a presynaptic role in synapse growth. We then harnessed the TARGET system to transiently express UAS (upstream activating sequence)– ben in a ben mutant background and identified a well defined critical period for Ben function in establishing a full-grown, mature synaptic terminal. We demonstrate that the protein must be present at a time point before but not during the actual growth process. We also provide phenotypic evidence demonstrating that Ben is not a part of the signal transduction pathway involving the well characterized ubiquitin ligase highwire . We conclude that Bendless functions as a novel developmental switch that permits the transition from axonal growth and incipient synapse formation to synaptic growth and maturation in the CNS.

Growth cone

Synaptogenesis

10.1523/jneurosci.2990-08.2008

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Citations (23)

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

Nature Neuroscience (2002)

Tanja A. Godenschwege Hailan Hu Xiaoliang Shan-Crofts Corey S. Goodman Rodney K. Murphey

Synapse formation

10.1038/nn976

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Citations (120)

Maps in the Insect Nervous System, Their Implications for Synaptic Connectivity and Target Location in the Real World

Springer eBooks (1983)

Rodney K. Murphey

Interneuron

10.1007/978-3-642-69271-0_13

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Citations (12)

Rearing in darkness changes visually-guided choice behavior in Drosophila

Visual Neuroscience (1990)

Helmut V. B. Hirsch Doreen Potter Dariusz Zawierucha Tanvir F. Choudhri Adrian Glasser

To test whether visual experience can affect development of visual behavior in the fruitfly, Drosophila, we measured the visually-guided choice behavior of groups of flies reared in complete darkness, compared with controls reared in a normal light/dark cycle. We used a simple visual preference test, i.e. choice among four different visual targets each consisting of vertical black lines of a particular width on a white background, using a blind testing procedure so that the individual rearing histories were not known by the tester. Both groups of flies were strongly attracted to the vertical lines; however, generally the dark-reared flies were more attracted to the wider stimulus lines than were the control flies. Control experiments in which normally reared adults were kept for several days in darkness showed that the effects of dark-rearing were not simply due to being in darkness, but depended upon the timing of the deprivation. The results indicate that the development of visual behavior can be affected by visual experience in Drosophila and thus open the possibility of using Drosophila for genetic dissection of mechanisms of visual plasticity.

Darkness

Stimulus (psychology)

10.1017/s0952523800000353

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Citations (31)

Netrin and Frazzled Regulate Presynaptic Gap Junctions at aDrosophilaGiant Synapse

Journal of Neuroscience (2014)

Brian O. Orr Melissa A. Borgen Phyllis M. Caruccio Rodney K. Murphey

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. When we examined the gap junctions with antibodies to Shaking-B (ShakB) Innexin, they were significantly decreased or absent in the presynaptic terminal of the mutant GF. Frazzled loss of function mutants exhibited similar defects in synaptic transmission, dye coupling, and gap junction localization. These data are the first to show that Netrin and Frazzled regulate the placement of gap junctions presynaptically at a synapse.

Netrin

Electrical Synapses

10.1523/jneurosci.3183-13.2014

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Citations (16)

The effect of neuronal growth on synaptic integration

Journal of Computational Neuroscience (1994)

Andrew A. Hill Donald H. Edwards Rodney K. Murphey

Stretch receptor

Allometry

Morphology

10.1007/bf00961736