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The Crone Laboratory studies how neural circuits controlling motor behaviors are affected by disease and injury. Our goal is to develop strategies targeting neural circuits capable of improving motor function and the quality of life of patients suffering from developmental defects, neurodegenerative disease or injury. Our focus is on the circuits in the spinal cord and brainstem that control walking and breathing and the diseases that affect them: including spinal muscular atrophy (SMA, “floppy baby syndrome”), amyotrophic lateral sclerosis (ALS, “Lou Gehrig’s Disease”), congenital central hypoventilation syndrome (CCHS, “Ondine’s curse”), and spinal cord injury.
To accomplish our goals, we use transgenic mouse and viral tools to label and manipulate specific neural populations in animal models of disease or injury. By manipulating the development or firing activity of specific interneurons, we determine how neural activity contributes to normal circuit development as well as to the onset and progression of disease. Using conditional mutant mice, we assess which changes in gene expression and which cell types are important for disease and recovery from injury. Our lab uses a wide range of techniques that look at neural circuits from the molecular and cellular level up to the level of physiology and behavior.
Our lab is also actively involved in the Neuromuscular Development Group. Our collaborations aim to accelerate research in the development and diseases of the neuromuscular system.
Image depicting the mouse spinal cord with motor neurons labeled using antibodies to non-phosphorylated neurofilaments.
Crone SA, Viemari J-C, Droho S, Ramirez J, Mrejeru A, Sharma K. Irregular breathing in mice following genetic ablation of V2a neurons. J Neurosci. 2012 Jun 6;32(23):7895-906.
Crone SA, Sharma K. Patterning spinal motor activity in the absence of synaptic excitation. Neuron. 2011 Sep 22;71(6):957-9.
Zhong G, Droho S, Crone SA, Dietz S, Kwan AC, Webb WW, Sharma K, Harris-Warrick R. Electrophysiological characterization of the V2a interneurons and their locomotor-related activity in the neonatal mouse spinal cord. J Neurosci. 2010 Jan 6;30(1):170-182.
Crone SA, Zhong G, Harris-Warrick R, Sharma K. In mice lacking V2a interneurons, gait depends on speed of locomotion. J Neurosci. 2009 May 27;29(21):7098-7109.
Crone SA, Quinlan KA, Zagoraiou L, Droho S, Restrepo CE, Lundfald L, Endo T, Setlak J, Jessell TM, Kiehn O, Sharma K. Genetic ablation of V2a ipsilateral interneurons disrupts left-right locomotor coordination in mammalian spinal cord. Neuron. 2008 Oct 9;60(1):70-83.
Joseph NM, Mukouyama Y, Mosher JT, Jaegle M, Crone SA, Dormand E, Lee K-F, Meijer D, Anderson DJ, Morrison SJ. Neural crest stem cells undergo multi-lineage differentiation in developing peripheral nerves to generate endoneurial fibroblasts in addition to Schwann cells. Development. 2004 Nov;131:5599-5612.
Crone SA, Negro A, Trumpp A, Giovannini M, Lee K-F. Colonic epithelial expression of ErbB2 is required for postnatal maintenance of the enteric nervous system. Neuron. 2003 Jan 9;37:29-40.
Crone SA, Zhao Y-Y, Fan L, Gu Y, Minamisawa S, Liu Y, Peterson KL, Chen J, Kahn R, Condorelli G, Ross J Jr, Chien KR, Lee K-F. ErbB2 is essential in the prevention of dilated cardiomyopathy. Nature Medicine. 2002;8:459-465.
Crone SA, Lee K-F. Gene targeting reveals multiple essential functions of the neuregulin signaling system during development of the neuroendocrine and nervous systems. Ann N Y Acad Sci. 2002 Oct;971:547-553.
Kaspar BK, Vissel B, Bengoechea T, Crone S, Randolph-Moore L, Muller R, Brandon EP, Schaffer D, Verma IM, Lee K-F, Heinemann SF, Gage FH. Adeno-associated virus effectively mediates conditional gene modification in the brain. Proceedings of the National Academy of Sciences USA. 2002;99:2320-5.
Crone SA, Zhao YY, Fan L, Gu Y, Minamisawa S, Liu Y, Peterson KL, Chen J, Kahn R, Condorelli G, Ross J Jr, Chien KR, Lee KF. ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med. 2002 May;8(5):459-65.
Crone SA, Lee KF. The bound leading the bound: target-derived receptors act as guidance cues. Neuron. 2002 Oct 24;36(3):333-5. Review.
Dr. Crone and his lab join Cincinnati Children's President and CEO, Michael Fisher, in taking the ALS Ice Bucket Challenge.
2014 Trustee AwardFrom Cincinnati Children's Hospital Medical Center
2013 Emerging Investigator AwardFightSMA!The Gwendolyn Strong Foundation
2013 Starter GrantAmyotrophic Lateral Sclerosis Association
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