Division of Developmental Neurobiology, Medical Research Council National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
Dev Cell. 2010 Jan 19;18(1):136-47. doi: 10.1016/j.devcel.2009.11.010.
Precise regulation of neurogenesis is achieved in specific regions of the vertebrate nervous system by formation of distinct neurogenic and nonneurogenic zones. We have investigated how neurogenesis becomes confined to zones adjacent to rhombomere boundaries in the zebrafish hindbrain. The nonneurogenic zone at segment centers comprises a distinct progenitor population that expresses fibroblast growth factor (fgfr) 2, erm, sox9b, and the retinoic acid degrading enzyme, cyp26b1. FGF receptor activation upregulates expression of these genes and inhibits neurogenesis in segment centers. Cyp26 activity is a key effector inhibiting neuronal differentiation, suggesting antagonistic interactions with retinoid signaling. We identify the critical FGF ligand, fgf20a, which is expressed by specific neurons located in the mantle region at the center of segments, adjacent to the nonneurogenic zone. Fgf20a mutants have ectopic neurogenesis and lack the segment center progenitor population. Our findings reveal how signaling from neurons induces formation of a nonneurogenic zone of neural progenitors.
脊椎动物神经系统的特定区域通过形成不同的神经发生和非神经发生区域来实现神经发生的精确调节。我们研究了神经发生如何局限于斑马鱼后脑的菱脑节边界附近的区域。位于节中心的非神经发生区包含一个独特的祖细胞群体，该群体表达成纤维细胞生长因子 (fgfr) 2、erm、sox9b 和视黄酸降解酶 cyp26b1。FGF 受体的激活上调了这些基因的表达，并抑制了节中心的神经发生。Cyp26 的活性是抑制神经元分化的关键效应物，表明与视黄酸信号存在拮抗相互作用。我们确定了关键的 FGF 配体 fgf20a，它由位于节中心的特定神经元表达，这些神经元位于节的中心，紧邻非神经发生区。Fgf20a 突变体具有异位神经发生，并且缺乏节中心祖细胞群体。我们的发现揭示了神经元发出的信号如何诱导神经前体细胞形成非神经发生区。
