Increased progenitor proliferation and apoptotic cell death in the sensory lineage of mice overexpressing N-myc.
N-myc, a member of the myc family of bHLH transcription factors, is expressed mainly in the nervous system, including derivatives of neural crest cells in the periphery during development, such as the sensory dorsal root ganglion (DRG). Previous studies suggest that N-myc is involved in the proliferation of progenitor cells in the sensory lineage. To address the role of N-myc in the development of peripheral sensory neurons, we have overexpressed N-myc in sensory progenitor cells. The overexpression of N-myc did not significantly affect the number of multipotent neural crest cells or glial differentiation but caused a brief and marked increase of both proliferation and apoptosis in the DRG at embryonic day 11 (E11), thus coinciding with the stage of cell-cycle exit. At E17, the total number of cells in the lumbar DRG of mice with forced expression of N-myc was significantly reduced compared with that in wild-type mice. Among the different DRG subpopulations examined, the number of parvalbumin-positive neurons representing large-diameter proprioceptive neurons increased significantly. Our results indicate that forced expression of N-myc in the sensory lineage leads to unscheduled cell-cycle re-entry and excessive apoptosis and show that N-myc can affect the composition of different functional subtypes of sensory neurons in the DRG.
Kobayashi
Miwako
M
Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Scheelesv. 1, 171 77 Stockholm, Sweden.
Hjerling-Leffler
Jens
J
Ernfors
Patrik
P
D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D049109:Cell Proliferation; D005121:Extremities / Q000294:innervation; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D009475:Neurons, Afferent / Q000378:metabolism* / Q000502:physiology*; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D013234:Stem Cells
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D016271:Proto-Oncogene Proteins c-myc