Waschek J A, Casillas R A, Nguyen T B, DiCicco-Bloom E M, Carpenter E M, Rodriguez W I
Department of Psychiatry, Mental Retardation Research Center, and Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90024-1759, USA.
Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9602-7. doi: 10.1073/pnas.95.16.9602.
Neural tube patterning in vertebrates is controlled in part by locally secreted factors that act in a paracrine manner on nearby cells to regulate proliferation and gene expression. We show here by in situ hybridization that genes for the neuropeptide pituitary adenylate cyclase-activating peptide (PACAP) and one of its high-affinity receptors (PAC1) are widely expressed in the mouse neural tube on embryonic day (E) 10.5. Transcripts for the ligand are present in differentiating neurons in much of the neural tube, whereas the receptor gene is expressed in the underlying ventricular zone, most prominently in the alar region and floor plate. PACAP potently increased cAMP levels more than 20-fold in cultured E10.5 hindbrain neuroepithelial cells, suggesting that PACAP activates protein kinase A (PKA) in the neural tube and might act in the process of patterning. Consistent with this possibility, PACAP down-regulated expression of the sonic hedgehog- and PKA-dependent target gene gli-1 in cultured neuroepithelial cells, concomitant with a decrease in DNA synthesis. PACAP is thus an early inducer of cAMP levels in the embryo and may act in the neural tube during patterning to control cell proliferation and gene expression.
脊椎动物的神经管模式形成部分受局部分泌因子控制，这些因子以旁分泌方式作用于附近细胞，调节细胞增殖和基因表达。我们通过原位杂交表明，神经肽垂体腺苷酸环化酶激活肽（PACAP）及其高亲和力受体之一（PAC1）的基因在胚胎第10.5天（E10.5）的小鼠神经管中广泛表达。配体的转录本存在于大部分神经管的分化神经元中，而受体基因则在其下方的脑室区表达，最显著的是在翼区和底板。PACAP能使培养的E10.5后脑神经上皮细胞中的cAMP水平有效升高20多倍，这表明PACAP在神经管中激活蛋白激酶A（PKA），并可能在模式形成过程中发挥作用。与此可能性一致的是，PACAP下调了培养的神经上皮细胞中依赖于音猬因子和PKA的靶基因gli-1的表达，同时DNA合成减少。因此，PACAP是胚胎中cAMP水平的早期诱导剂，可能在神经管模式形成过程中发挥作用，以控制细胞增殖和基因表达。
