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Publication : MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling.

First Author  Ka M Year  2014
Journal  Dev Biol Volume  395
Issue  1 Pages  4-18
PubMed ID  25224226 Mgi Jnum  J:216503
Mgi Id  MGI:5608925 Doi  10.1016/j.ydbio.2014.09.009
Citation  Ka M, et al. (2014) MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling. Dev Biol 395(1):4-18
abstractText  Neuronal migration and subsequent differentiation play critical roles for establishing functional neural circuitry in the developing brain. However, the molecular mechanisms that regulate these processes are poorly understood. Here, we show that microtubule actin crosslinking factor 1 (MACF1) determines neuronal positioning by regulating microtubule dynamics and mediating GSK-3 signaling during brain development. First, using MACF1 floxed allele mice and in utero gene manipulation, we find that MACF1 deletion suppresses migration of cortical pyramidal neurons and results in aberrant neuronal positioning in the developing brain. The cell autonomous deficit in migration is associated with abnormal dynamics of leading processes and centrosomes. Furthermore, microtubule stability is severely damaged in neurons lacking MACF1, resulting in abnormal microtubule dynamics. Finally, MACF1 interacts with and mediates GSK-3 signaling in developing neurons. Our findings establish a cellular mechanism underlying neuronal migration and provide insights into the regulation of cytoskeleton dynamics in developing neurons.
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