Loeb J A, Khurana T S, Robbins J T, Yee A G, Fischbach G D
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Development. 1999 Feb;126(4):781-91. doi: 10.1242/dev.126.4.781.
We mapped the distribution of neuregulin and its transmembrane precursor in developing, embryonic chick and mouse spinal cord. Neuregulin mRNA and protein were expressed in motor and sensory neurons shortly after their birth and levels steadily increased during development. Expression of the neuregulin precursor was highest in motor and sensory neuron cell bodies and axons, while soluble, released neuregulin accumulated along early motor and sensory axons, radial glia, spinal axonal tracts and neuroepithelial cells through associations with heparan sulfate proteoglycans. Neuregulin accumulation in the synaptic basal lamina of neuromuscular junctions occurred significantly later, coincident with a reorganization of muscle extracellular matrix resulting in a relative concentration of heparan sulfate proteoglycans at endplates. These results demonstrate an early axonal presence of neuregulin and its transmembrane precursor at developing synapses and a role for heparan sulfate proteoglycans in regulating the temporal and spatial sites of soluble neuregulin accumulation during development.
我们绘制了神经调节蛋白及其跨膜前体在发育中的鸡胚和小鼠脊髓中的分布情况。神经调节蛋白mRNA和蛋白在运动神经元和感觉神经元出生后不久即开始表达，且在发育过程中水平稳步上升。神经调节蛋白前体在运动和感觉神经元细胞体及轴突中的表达最高，而可溶性、释放型神经调节蛋白则通过与硫酸乙酰肝素蛋白聚糖结合，沿早期运动和感觉轴突、放射状胶质细胞、脊髓轴突束和神经上皮细胞积累。神经调节蛋白在神经肌肉接头突触基底膜中的积累明显较晚，与肌肉细胞外基质的重组同时发生，导致终板处硫酸乙酰肝素蛋白聚糖相对浓缩。这些结果表明，在发育中的突触处，神经调节蛋白及其跨膜前体早期存在于轴突中，且硫酸乙酰肝素蛋白聚糖在发育过程中调节可溶性神经调节蛋白积累的时间和空间位点方面发挥作用。
