Memberg S P, Hall A K
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
J Neurobiol. 1995 May;27(1):26-43. doi: 10.1002/neu.480270104.
Neuronal differentiation involves specific molecular and morphological changes in precursors and results in mature, postmitotic neurons. The expression of neuron-specific beta tubulin, as detected by the monoclonal antibody TuJ1, begins during the period of neurogenesis. Indeed, TuJ1 expression precedes that of the 160 kD neurofilament protein in both the central and peripheral nervous systems. In the embryonic rat spinal cord, bipolar cells and some mitotic cells in the ventricular zone were TuJ1 immunoreactive (IR). Sensory ganglia also contained cells with TuJ1-IR mitotic spindles in situ. In embryonic rat sensory and sympathetic ganglion cell cultures pulsed with the thymidine analog bromodeoxyuridine (BrdU), TuJ1 label was detected in the spindle of mitotic cells and in the midbody of cells joined at cytokinesis, indicating that neuron-specific tubulin expression was initiated during or before the final mitosis of neuronal progenitors. Dorsal root ganglion cultures included TuJ1-IR cells with several shapes that may reflect morphological transitions, from flattened stellate neural crest-like cells to differentiated bipolar neurons. Indeed, the presence of flattened TuJ1-IR cells was correlated with neurogenesis. Some sympathetic neuron precursors possessed long TuJ1-IR neurites, as well as TuJ1-IR spindle microtubules and BrdU-labeled chromosomes, indicating that these precursors can possess long processes during metaphase. These results support the hypothesis that neuron-specific tubulin expression represents an early molecular event in neuronal differentiation exhibited by a wide range of neuronal precursors. The cessation of proliferation can occur at different points during neuronal differentiation, as TuJ1-IR was detected in cells undergoing mitosis. Future studies directed toward understanding the molecules that initiate neuron-specific tubulin expression may lead to the factors that control the initial phases of neuronal differentiation.
神经元分化涉及前体细胞中特定的分子和形态变化，并产生成熟的、不再进行有丝分裂的神经元。通过单克隆抗体TuJ1检测到的神经元特异性β微管蛋白的表达在神经发生期开始。实际上，在中枢和外周神经系统中，TuJ1的表达都先于160 kD神经丝蛋白的表达。在胚胎大鼠脊髓中，双极细胞和室管膜区的一些有丝分裂细胞呈TuJ1免疫反应性（IR）。感觉神经节原位也含有具有TuJ1-IR有丝分裂纺锤体的细胞。在用胸苷类似物溴脱氧尿苷（BrdU）脉冲处理的胚胎大鼠感觉和交感神经节细胞培养物中，在有丝分裂细胞的纺锤体和胞质分裂时相连细胞的中间体中检测到TuJ1标记，表明神经元特异性微管蛋白表达在神经元祖细胞的最后一次有丝分裂期间或之前开始。背根神经节培养物中包括几种形状的TuJ1-IR细胞，这些形状可能反映了从扁平的星状神经嵴样细胞到分化的双极神经元的形态转变。实际上，扁平的TuJ1-IR细胞与神经发生相关。一些交感神经元前体具有长的TuJ1-IR神经突，以及TuJ1-IR纺锤体微管和BrdU标记的染色体，表明这些前体在中期可以具有长的突起。这些结果支持了这样的假设：神经元特异性微管蛋白表达代表了广泛的神经元前体所表现出的神经元分化中的早期分子事件。增殖的停止可能发生在神经元分化的不同阶段，因为在进行有丝分裂的细胞中检测到了TuJ1-IR。旨在了解启动神经元特异性微管蛋白表达的分子的未来研究可能会揭示控制神经元分化初始阶段的因素。
