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The major focus of my lab is to understand molecular cues that control the radia l growth of axons and death of motor neurons. Radial growth of axons is studied in mice by ES cell mediated homologous recombination. Motor neurons disease is s tudied in mouse models of amyotrophic lateral sclerosis (ALS) in transgenic mice for neurofilaments and superoxide dismutase 1 (SOD1). During development, axons undergo two major changes. First, the long, thin axons make growth cones and establish stable synapses. Second, axonal volume increase s 100 fold, and large myelinated axons accumulate large numbers of neurofilament s (NFs). NFs are 10 nm filaments composed of NF-H (200 kd), NF-M (150 kd) and N F-L (68 kd) subunits. Genetic analysis has shown a direct correlation between t he number of filaments and axonal volume. Our transgenic mouse models have indi cated that subunit ratios play a critical role in controlling radial growth of a xons. Recent gene deletion analysis on individual subunits indicate that NF-L i s important for filament formation; NF-M is important for filament assembly and control of filament number. In order to identify the domains of NF subunits tha t are responsible for controlling the radial growth of axons, a systematic domai n deletion approach is being used. We have successfully produced mice for carbox yl terminal deletions of NF-M and NF-H, and analyses of these mice are in progre ss.
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Nature Neuroscienceno. 6 (2022): 688-701
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Aidong Yuan, Veeranna,Henry Sershen,Balapal S. Basavarajappa,John F. Smiley,Audrey Hashim,Cynthia Bleiwas,Martin Berg, David N. Guifoyle,Shivakumar Subbanna,Sandipkumar Darji,Asok Kumar,
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