Neural tube expression of pituitary adenylate cyclase-activating peptide (PACAP) and receptor: Potential role in patterning and neurogenesis
Neural tube expression of pituitary adenylate cyclase-activating peptide (PACAP) and receptor: Potential role in patterning and neurogenesis
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DOI：
10.1073/pnas.95.16.9602
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发表时间：
1998-08-04
影响因子：
11.1
通讯作者：
Rodriguez, WI
中科院分区：
文献类型：
--
作者：
Waschek, JA;Casillas, RA;Rodriguez, WI
脊椎动物的神经管模式部分受到局部分泌因子的控制，这些因子以旁分泌方式作用于附近的细胞，以调节增殖和基因表达。我们在此通过原位杂交表明，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（PAC（1））的基因在胚胎（E）10.5天的小鼠神经管中广泛表达，转录本配体存在于大部分神经管的分化神经元中，而受体基因在下面的心室区表达，最明显的是在翼区和底板，PACAP 在培养的 E10.5 后脑神经上皮细胞中有效地将 cAMP 水平提高了 20 倍以上，表明 PACAP 激活神经管中的蛋白激酶 A (PKA)，并可能在模式化过程中发挥作用。与这种可能性相一致的是，PACAP 下调了培养的神经上皮细胞中 sonic hedgehog 和 PKA 依赖性靶标 gli-1 的表达，同时伴随着 DNA 合成的减少。因此，PACAP 是胚胎中 cAMP 水平的早期诱导剂，并且可能在模式形成过程中在神经管中发挥作用，以控制细胞增殖和基因表达。
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 (PAC(1)) 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 gent gli-l 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.