Erzurumlu R S, Jhaveri S, Takahashi H, McKay R D
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7235-9. doi: 10.1073/pnas.90.15.7235.
Cellular and molecular signals involved in axon elongation versus collateral and arbor formation may be intrinsic to developing neurons, or they may derive from targets. To identify signals regulating axon growth modes, we have developed a culture system in which trigeminal ganglion cells are challenged by various target tissues. Embryonic day 15 (E15) rat trigeminal ganglion explants were placed between peripheral (vibrissa pad) and central nervous system targets. Normally, bipolar trigeminal ganglion cells extend one process to the vibrissa pad and another to the brainstem trigeminal complex. Under coculture conditions, the peripheral processes invade the vibrissa pad explants and form a characteristic circumfollicular pattern. Central processes of E15 ganglion cells invade many, but not all, central nervous system tissues. In isochronic (E15) central nervous system explants such as brainstem, olfactory bulb, or neocortex, these central processes elongate and form a "tract" but have virtually no arbors. However, in more mature targets (e.g., a section from postnatal brainstem or neocortex), they form arbors instead of a tract. We conclude from these observations that whether trigeminal axons elongate to form a tract, or whether they begin to arborize, is dictated by the target tissue and not by an intrinsic developmental program of the ganglion cell body. The explant coculture system is an excellent model for analysis of the molecular basis of neuron-target interactions.
参与轴突延伸与侧支及分支形成的细胞和分子信号可能是发育中神经元所固有的,也可能源自靶标。为了确定调节轴突生长模式的信号,我们开发了一种培养系统,其中三叉神经节细胞受到各种靶组织的刺激。将胚胎第15天(E15)大鼠三叉神经节外植体置于外周(触须垫)和中枢神经系统靶标之间。正常情况下,双极三叉神经节细胞伸出一个突起至触须垫,另一个突起至脑干三叉神经复合体。在共培养条件下,外周突起侵入触须垫外植体并形成特征性的滤泡周围模式。E15神经节细胞的中枢突起侵入许多但并非所有的中枢神经系统组织。在等时(E15)中枢神经系统外植体如脑干、嗅球或新皮层中,这些中枢突起伸长并形成“束”,但几乎没有分支。然而,在更成熟的靶标(如出生后脑干或新皮层的切片)中,它们形成分支而不是束。我们从这些观察结果得出结论,三叉神经轴突是伸长形成束,还是开始分支,取决于靶组织,而不是神经节细胞体的内在发育程序。外植体共培养系统是分析神经元 - 靶标相互作用分子基础的极佳模型。