Associate Professor

Department of Neuroscience and
Center for Molecular Neurobiology

Ph.D.: Case Western Reserve University
Post-doctoral Training: University of Oregon

Center for Molecular Neurobiology
The Ohio State University
190 Rightmire Hall
1060 Carmack Road
Columbus, OH 43210

Phone: 614-292-5113
Fax: 614-292-5379
E-mail:Beattie.24@osu.edu
Lab website: http://www.neurobiotech.ohio-state.edu/ChristineBeattieLab/home.asp
Zebrafish Facility website: http://www.neurobiotech.ohio-state.edu/ChristineBeattieLab/html/fishfacility.asp

Link to NLM & NIH PubMed publications list for Christine Beattie (last 10 years)

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Research Area:

• Molecular mechanisms controlling vertebrate axon guidance during development and disease using zebrafish as a model system.

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Research Description:

The generation of neuromuscular specificity depends on motor axons growing to and innervating the correct target muscles. Growth cones pathfind towards their targets in a highly stereotyped manner making few navigational errors. While numerous motor axon pathways in vertebrates have been described at the cellular level, little is known about the genes that regulate stereotyped pathfinding events. One of the main focuses of the lab is to elucidate the mechanisms and molecules that control motor axon guidance in vertebrates. To this end, we have isolated mutations that disrupt motor axon guidance in the zebrafish. Zebrafish is an excellent model system for studying vertebrate motor axon guidance due to its relatively simple, early nervous system, rapid development and the ability to induce, recover and clone mutations. We are studying two mutations, stumpy and topped, that dramatically and specifically affect motor axons. Mutations in the stumpy gene cause motor axons to stall at intermediate targets and to fail to extend into distal target regions. This gene acts both in neurons and in the environment to enable growth cones to proceed past intermediate targets. We are in the process of cloning this gene to understand how it is functioning. topped mutants also have a stall defect, but only ventral motor axons are affected. Genetic mosaic analysis reveals that topped function is only needed in ventromedial myotome cells suggesting that topped is a ventral cue for motor axons. Studying these and other mutations that affect motor axon guidance enables us to build genetic pathways that define motor axon outgrowth.

We are also interested in motoneuron diseases and have been collaborating with Dr. Arthur Burghes (Molecular and Cellular Biochemistry Department) to model Spinal Muscular Atrophy (SMA) in zebrafish. SMA is an autosomal recessive disorder characterized by a loss of alpha-motoneurons in the spinal cord. SMA is caused by low levels of the ubiquitously expressed survival motor neuron (Smn) protein. As it is unclear how low levels of Smn specifically affect motoneurons, we have knocked-down Smn protein levels in zebrafish. In doing so, we found specific defects in motor axons. These included axon branching and axon truncations. Reduction of Smn in individual motoneurons revealed that smn is acting cell-autonomously. These results show for the first time, in vivo, that Smn functions in motor axon development and suggest that these early developmental defects may lead to subsequent motoneuron loss. Our goal now is to determine the function of Smn is motoneurons and to elucidate why and how this is causing motoneurons cell death. 

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Techniques and Models:

• Genetics (inducing and recovering mutations)
• Gene cloning
• Protein knock-down with antisense morpholinos
• Microscopy (confocal and compound)
• Making transgenic zebrafish