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Michael B. O'Connor, Ph.D. Professor, Department of Genetics, Cell Biology and Development Associate Investigator, Howard Hughes Medical Institute Ordway Professor of Developmental biology E-mail: moconnor@umn.edu O'Connor Lab Web Site

Research Interests:

During the development of all animals, tissues must grow in a coordinated manner in order to function properly as integrated units within the adult. This is especially important during neuronal wiring. In the case of motoneurons, axons must project over large distances, find a specific target muscle and then maintain appropriate synaptic efficacy during subsequent growth. The latter issue is particularly important during Drosophila neuromuscular development since the muscle volume increases up to 100 fold during larval growth. An inability to coordinate synapse growth with this rapid increase in muscle volume would likely lead to severe impairment of motor control. Remarkably, we have found that BMP signaling regulates the growth and function of the synapse at the Drosophila neuromuscular junction (NMJ). This discovery came from studying the phenotype of mutations in the wishful thinking (wit) gene, a Drosophila homolog of the vertebrate BMP type II receptor. Mutations in wit lead to pharate lethality as a result of an inability of adult animals to escape from the pupal case. We showed that this phenotype is caused by reduced growth of motoneuron synapses at the NMJ and severe defects in neurotransmission. We also found that Gbb, a BMP 5/6/7 homolog, signals in a retrograde manner (from the muscle to the neuron) to regulate synaptic size and function at the Drosophila NMJ. Our present goal is to use micro array and genetic methodologies to try and identify the downstream target genes in the motorneurons that are regulated by BMP signaling.

Since BMPs are heavily expressed in the vertebrate brain, especially the hippocampus, we have also begun studies in the mouse to address whether BMP signaling regulates synaptic plasticity in the hippocampus. Using gain of function studies we have found that excess BMP signaling enhances paired-pulse facilitation (PPF), long term potentiaion (LTP) and learning in a Morris water maze paradigm. Conversely, loss of BMP signaling reduces PPF, LTP and leads to poor learning. We are presently trying to determine the molecular basis for how BMP signaling modulates these properties

Selected Publications:

(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)

Ting CY, Herman T, Yonekura S, Gao S, Wang J, Serpe M, O'Connor MB, Zipursky SL, Lee CH. Tiling of r7 axons in the Drosophila visual system is mediated both by transduction of an activin signal to the nucleus and by mutual repulsion. Neuron. 2007 Dec 6;56(5):793-806.

McBrayer Z, Ono H, Shimell M, Parvy JP, Beckstead RB, Warren JT, Thummel CS, Dauphin-Villemant C, Gilbert LI, O'Connor MB. Prothoracicotropic hormone regulates developmental timing and body size in Drosophila. Dev Cell. 2007 Dec;13(6):857-71.

Rewitz KF, O'Connor MB, Gilbert LI. Molecular evolution of the insect Halloween family of cytochrome P450s: phylogeny, gene organization and functional conservation. Insect Biochem Mol Biol. 2007 Aug;37(8):741-53. Epub 2007 Mar 5.

Sun M, Thomas MJ, Herder R, Bofenkamp ML, Selleck SB, O'Connor MB. Presynaptic contributions of chordin to hippocampal plasticity and spatial learning. J Neurosci. 2007 Jul 18;27(29):7740-50.

Knox S, Ge H, Dimitroff BD, Ren Y, Howe KA, Arsham AM, Easterday MC, Neufeld TP, O'Connor MB, Selleck SB. Mechanisms of TSC-mediated control of synapse assembly and axon guidance. PLoS ONE. 2007 Apr 18;2(4):e375.

Umulis D, O'Connor MB, Othmer HG. 2 Robustness of Embryonic Spatial Patterning in Drosophila melanogaster. Curr Top Dev Biol. 2007;81:65-111.

Serpe M, O'Connor MB. The metalloprotease tolloid-related and its TGF-beta-like substrate Dawdle regulate Drosophila motoneuron axon guidance. Development. 2006 Dec;133(24):4969-79.

Takaesu NT, Hyman-Walsh C, Ye Y, Wisotzkey RG, Stinchfield MJ, O'connor MB, Wotton D, Newfeld SJ. dSno facilitates baboon signaling in the Drosophila brain by switching the affinity of Medea away from Mad and toward dSmad2. Genetics. 2006 Nov;174(3):1299-313.

Ono H, Rewitz KF, Shinoda T, Itoyama K, Petryk A, Rybczynski R, Jarcho M, Warren JT, Marques G, Shimell MJ, Gilbert LI, O'Connor MB. Spook and Spookier code for stage-specific components of the ecdysone biosynthetic pathway in Diptera. Dev Biol. 2006 Oct 15;298(2):555-70.

Umulis DM, Serpe M, O'Connor MB, Othmer HG.   Robust, bistable patterning of the dorsal surface of the Drosophila embryo. Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11613-8.

Jadrich JL, O'Connor MB, Coucouvanis E. The TGF beta activated kinase TAK1 regulates vascular development in vivo. Development. 2006 Apr;133(8):1529-41.

O'Connor MB, Umulis D, Othmer HG, Blair SS. Shaping BMP morphogen gradients in the Drosophila embryo and pupal wing. Development. 2006 Jan;133(2):183-93. Review.