Kobayashi Miwako, Hjerling-Leffler Jens, Ernfors Patrik
Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Scheelesv. 1, 171 77 Stockholm, Sweden.
Cell Tissue Res. 2006 Jan;323(1):81-90. doi: 10.1007/s00441-005-0011-5. Epub 2005 Aug 13.
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.
N-myc是bHLH转录因子myc家族的成员之一，主要在神经系统中表达，包括发育过程中外周神经嵴细胞的衍生物，如感觉背根神经节（DRG）。先前的研究表明，N-myc参与感觉谱系中祖细胞的增殖。为了研究N-myc在外周感觉神经元发育中的作用，我们在感觉祖细胞中过表达了N-myc。N-myc的过表达对多能神经嵴细胞的数量或胶质细胞分化没有显著影响，但在胚胎第11天（E11）导致DRG中增殖和凋亡短暂而显著增加，这与细胞周期退出阶段一致。在E17时，与野生型小鼠相比，强制表达N-myc的小鼠腰段DRG中的细胞总数显著减少。在所检测的不同DRG亚群中，代表大直径本体感觉神经元的小白蛋白阳性神经元数量显著增加。我们的结果表明，在感觉谱系中强制表达N-myc会导致细胞周期意外重新进入和过度凋亡，并表明N-myc可影响DRG中不同功能亚型感觉神经元的组成。
