ElShamy W M, Linnarsson S, Lee K F, Jaenisch R, Ernfors P
Department of Medical Biochemistry and Biophysics, Laboratory of Molecular Neurobiology, Karolinska Institute, Stockholm, Sweden.
Development. 1996 Feb;122(2):491-500. doi: 10.1242/dev.122.2.491.
Postnatal homozygous neurotrophin-3 mutant mice display a loss of about half the sympathetic superior cervical ganglion (SCG) neurons (Ernfors, P., Lee, K.-F., Kucera, J. and Jaenisch, R. (1994a) Cell 77, 503-512; Farinas, I., Jones, K. R., Backus, C., Wang, X. Y. and Reichardt, L. F. (1994) Nature 369, 658-661). We found that this loss is caused by excessive apoptosis of sympathetic neuroblasts leading to a failure to generate a normal number of neurons during neurogenesis. NT-3 was also found to be required postnatally. In Nt-3-/- mice, sympathetic fibers failed to invade pineal gland and external ear postnatally; whereas other targets of the external and internal carotid nerves, including the submandibular gland and the iris, displayed a normal complement of sympathetic innervation. Sympathetic fibers of mice carrying one functional copy of the Nt-3 gene (Nt-3+/- mice) invaded the pineal gland, but failed to branch and form a ground plexus. Cultured neonatal sympathetic neurons responded to NT-3 by neurite outgrowth and mRNA upregulation of the NT-3 receptor, trkC. Exogenously administered NT-3 promoted sympathetic growth and rescued the sympathetic target deficit of the mutant mice. We conclude that NT-3 is required for the survival of sympathetic neuroblasts during neurogenesis and for sympathetic innervation and branching in specific targets after birth.
出生后的纯合神经营养因子-3突变小鼠显示，交感神经颈上神经节（SCG）神经元损失约一半（厄恩福斯，P.，李，K.-F.，库切拉，J.和亚尼什，R.（1994a）《细胞》77卷，503 - 512页；法里纳斯，I.，琼斯，K. R.，巴克斯，C.，王，X. Y.和赖夏德特，L. F.（1994）《自然》369卷，658 - 661页）。我们发现这种损失是由交感神经母细胞过度凋亡导致的，从而在神经发生过程中无法产生正常数量的神经元。还发现出生后也需要NT - 3。在Nt - 3 - / -小鼠中，交感神经纤维在出生后未能侵入松果体和外耳；而颈外和颈内神经的其他靶器官，包括下颌下腺和虹膜，显示出正常的交感神经支配。携带Nt - 3基因一个功能拷贝的小鼠（Nt - 3 + / -小鼠）的交感神经纤维侵入了松果体，但未能分支并形成基层神经丛。培养的新生交感神经元对NT - 3有反应，表现为神经突生长和NT - 3受体trkC的mRNA上调。外源性给予NT - 3促进了交感神经生长，并挽救了突变小鼠的交感神经靶器官缺陷。我们得出结论，NT - 3在神经发生过程中对交感神经母细胞的存活以及出生后特定靶器官的交感神经支配和分支是必需的。
