Lentz S I, Miner J H, Sanes J R, Snider W D
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Comp Neurol. 1997 Feb 24;378(4):547-61. doi: 10.1002/(sici)1096-9861(19970224)378:4<547::aid-cne9>3.0.co;2-2.
Laminins are heterotrimers of alpha, beta, and gamma chains. At present, five alpha, three beta, and two gamma chains have been described. The best characterized laminin (laminin 1 = alpha 1, beta 1, gamma 1) promotes neurite outgrowth from virtually all classes of developing neurons, implying that laminins may serve as axon guidance molecules in vivo. Moreover, different laminin trimers exert distinct effects on subsets of laminin-1-responsive cells, suggesting that isoform diversity may underlie some axonal choices in vivo. As a first step toward evaluating these hypotheses, we have documented the expression patterns of all 10-known laminin chains in the peripheral nervous system and spinal cord of the murine embryo. The alpha 2, alpha 4, beta 1, and gamma 1 chains are expressed in peripheral axonal pathways by embryonic day (E) 11.5, when sensory and motor axonal outgrowth is underway. Thus, laminins (but not laminin 1) may promote peripheral axonal outgrowth. By E 13.5, laminin chains are differentially expressed in the limb-bud, with prominent expression of alpha 2 and alpha 4 in muscle and of alpha 3 and alpha 5 in skin. This pattern raises the possibility that laminin isoform diversity contributes to the ability of cutaneous and muscle sensory axons to distinguish their targets. Later in development, some chains (e.g., alpha 2, alpha 4, and beta 1) are downregulated in peripheral nerve while others (e.g., gamma 1), continue to be expressed by Schwann cells into adulthood. In contrast to peripheral nerves and ganglia, laminin chains are expressed at low levels, if at all, in the developing spinal cord gray matter.
层粘连蛋白是由α、β和γ链组成的异源三聚体。目前,已描述了5种α链、3种β链和2种γ链。特征最明确的层粘连蛋白(层粘连蛋白1 = α1、β1、γ1)能促进几乎所有类型发育中神经元的轴突生长,这意味着层粘连蛋白可能在体内作为轴突导向分子发挥作用。此外,不同的层粘连蛋白三聚体对层粘连蛋白1反应性细胞亚群有不同影响,表明异构体多样性可能是体内某些轴突选择的基础。作为评估这些假设的第一步,我们记录了小鼠胚胎外周神经系统和脊髓中所有10种已知层粘连蛋白链的表达模式。α2、α4、β1和γ1链在胚胎第(E)11.5天在周围轴突通路中表达,此时感觉和运动轴突正在生长。因此,层粘连蛋白(而非层粘连蛋白1)可能促进周围轴突生长。到E 13.5时,层粘连蛋白链在肢芽中差异表达,α2和α4在肌肉中显著表达,α3和α5在皮肤中显著表达。这种模式增加了层粘连蛋白异构体多样性有助于皮肤和肌肉感觉轴突区分其靶标的可能性。在发育后期,一些链(如α2、α4和β1)在周围神经中下调,而其他链(如γ1)在成年期仍由施万细胞持续表达。与周围神经和神经节不同,层粘连蛋白链在发育中的脊髓灰质中即使有表达也处于低水平。