ElShamy W M, Ernfors P
Department of Medical Biochemistry and Biophysics, Laboratory of Molecular Neurobiology, Karolinska Institute, Stockholm, Sweden.
Neuron. 1996 May;16(5):963-72. doi: 10.1016/s0896-6273(00)80119-1.
The role of neurotrophin-3 (NT-3) in early development of the dorsal root ganglion was investigated. Excessive cell death in the dorsal root ganglion of mice that carry a deleted NT-3 gene (NT-3-/- mice) preceded the period of programmed cell death, detected by the TUNEL method, and caused a reduction in the number of proliferating precursors without altering the proportion of proliferating cells to total number of neurons. Furthermore, the majority of proliferating cells detected by bromodeoxyuridine incorporation also stained with the TUNEL method. NT-3 mRNA was expressed locally in the embryonic, but not the postnatal dorsal root ganglion. Most cultured early embryonic NT-3-/- neurons died in the absence of exogenous NT-3 as did the wild-type neurons when cultured with NT-3 neutralizing antibodies, suggesting that NT-3 acts locally to prevent the death of proliferating sensory precursor cells during neurogenesis. Thus, NT-3 may inflict constraints on the number of proliferating precursor cells and thereby affect the number of neurons generated during development of the peripheral nervous system.
研究了神经营养因子-3（NT-3）在背根神经节早期发育中的作用。通过TUNEL法检测发现，携带缺失NT-3基因的小鼠（NT-3-/-小鼠）背根神经节中过量的细胞死亡先于程序性细胞死亡期，并导致增殖前体细胞数量减少，而未改变增殖细胞占神经元总数的比例。此外，通过溴脱氧尿苷掺入法检测到的大多数增殖细胞也能用TUNEL法染色。NT-3 mRNA在胚胎期背根神经节中局部表达，但在出生后不表达。大多数培养的早期胚胎NT-3-/-神经元在没有外源性NT-3的情况下死亡，与野生型神经元在用NT-3中和抗体培养时的情况相同，这表明NT-3在神经发生过程中局部发挥作用，防止增殖的感觉前体细胞死亡。因此，NT-3可能会限制增殖前体细胞的数量，从而影响外周神经系统发育过程中产生的神经元数量。
