Landmesser L, Dahm L, Schultz K, Rutishauser U
Department of Physiology and Neurobiology, University of Connecticut, Storrs 06268.
Dev Biol. 1988 Dec;130(2):645-70. doi: 10.1016/0012-1606(88)90358-2.
In vitro studies have suggested that the cell adhesion molecules NCAM and G4/L1 contribute to a variety of events during neural development. We have directly tested the role played by these molecules in the process of initial nerve ingrowth and ramification in the embryonic chick iliofibularis muscle by in ovo injections of specific adhesion-blocking antibodies and analysis of the resultant nerve branching pattern in muscle whole mounts. Antibodies against both molecules produced axonal defasciculation, which resulted in an enhanced transverse projection to the fast region of the muscle. In the case of anti-G4/L1, we also observed a large increase in the number of side branches that form from nerve trunks in the slow region and an enhancement of nerve branching in the fast region. Conversely, anti-NCAM produced a striking decrease in both the number and length of side branches in the slow region, and a reduction in nerve branching in the fast region. A similar reduction of nerve branching was obtained following injection of an endosialidase, which removes sialic acid from NCAM, and which was observed to enhance fiber-fiber apposition, presumably by increasing cell adhesion. Based on their biochemical properties in vitro and their in vivo distribution, both NCAM and G4/L1 are in a position to contribute to axon-axon adhesive interactions, whereas NCAM would be expected to also promote axon-myotube interactions. Our observations in fact indicate that these two adhesion molecules play different but complementary roles during muscle innervation and, specifically, that axon-axon fasciculation is influenced by both NCAM and G4/L1 in an anatomically distinct manner to regulate the overall pattern of nerve branching and that NCAM-mediated axon-myotube interactions are necessary for the attainment of the normal stereotyped pattern of nerve branching in both fast and slow regions of this muscle.
体外研究表明，细胞黏附分子NCAM和G4/L1在神经发育过程中参与了多种事件。我们通过在鸡胚卵内注射特异性黏附阻断抗体，并分析肌肉整装标本中由此产生的神经分支模式，直接测试了这些分子在胚胎期鸡髂腓肌初始神经长入和分支过程中所起的作用。针对这两种分子的抗体均导致轴突解束，从而增强了向肌肉快速区域的横向投射。对于抗G4/L1抗体，我们还观察到慢区域神经干形成的侧支数量大幅增加，以及快区域神经分支增强。相反，抗NCAM抗体使慢区域侧支的数量和长度均显著减少，快区域神经分支也减少。注射一种能从NCAM上去除唾液酸的内切唾液酸酶后，也观察到类似的神经分支减少，且据推测这是通过增加细胞黏附来增强纤维-纤维附着。基于它们在体外的生化特性及其体内分布，NCAM和G4/L1均有可能参与轴突-轴突黏附相互作用，而预计NCAM还会促进轴突-肌管相互作用。我们的观察结果实际上表明，这两种黏附分子在肌肉神经支配过程中发挥着不同但互补的作用，具体而言，轴突-轴突束化受到NCAM和G4/L1的影响，其方式在解剖学上有所不同，以调节神经分支的整体模式，并且NCAM介导的轴突-肌管相互作用对于在该肌肉的快、慢区域获得正常的定型神经分支模式是必要的。
