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Publication : Requirement of N-myc protein down-regulation for neuronal differentiation in the spinal cord.

First Author  Shimono A Year  1996
Journal  Dev Growth Differ Volume  38
Issue  6 Pages  707-716
Mgi Jnum  J:38017 Mgi Id  MGI:85410
Doi  10.1046/j.1440-169X.1996.t01-1-00014.x Citation  Shimono A, et al. (1996) Requirement of N-myc protein down-regulation for neuronal differentiation in the spinal cord. Dev Growth Differ 38(6):707-716
abstractText  Previous work has indicated that N-myc expression occurs widely in the developing central nervous system, but its level changes dynamically with region- and stage- specificities. We show in the present report that in the developing spinal cord of the mouse, N-myc protein expression takes place in the ventricular zone and reaches its maximum at the outermost layer, but is extinct in the intermediate zone, indicating that N-myc protein is not expressed in mature neurons. We examined the effect of forced, persistent N-myc expression in development of the spinal cord in order to understand the functional significance of N-myc down-regulation. We made embryonic stem (ES) cell lines that constitutively expressed N-myc at a high level, then produced mouse embryo chimeras with a high contribution of the ES cells. The majority of the chimeras developed to day 12 with normal gross morphology, but in these chimeras neuronal differentiation ih the spinal Cord was perturbed at the histological level, Intermediate zones and ventral horns were formed, but the expression of N-CAM and neurofilaments was diminished. Chimeras using beta-galactosidase-expressing recipient embryos indicated that inhibition of the neuronal differentiation was a cell-autonomous effect of persistent N-myc expression. These observations indicate that N-myc down-regulation in individual cells is required for full differentiation of neurons.
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