Graduate Program in Neurobiology and Behavior, University of Washington, Seattle, WA 98195-7420, USA.
Development. 2012 Mar;139(6):1141-52. doi: 10.1242/dev.072439. Epub 2012 Feb 1.
The neural crest is a migratory, multipotent cell lineage that contributes to myriad tissues, including sensory neurons and glia of the dorsal root ganglia (DRG). To identify genes affecting cell fate specification in neural crest, we performed a forward genetic screen for mutations causing DRG deficiencies in zebrafish. This screen yielded a mutant lacking all DRG, which we named sensory deprived (sdp). We identified a total of four alleles of sdp, all of which possess lesions in the gene coding for reversion-inducing cysteine-rich protein containing Kazal motifs (Reck). Reck is an inhibitor of metalloproteinases previously shown to regulate cell motility. We found reck function to be both necessary for DRG formation and sufficient to rescue the sdp phenotype. reck is expressed in neural crest cells and is required in a cell-autonomous fashion for appropriate sensory neuron formation. In the absence of reck function, sensory neuron precursors fail to migrate to the position of the DRG, suggesting that this molecule is crucial for proper migration and differentiation.
神经嵴是一种迁移的、多能的细胞谱系，它有助于形成多种组织，包括背根神经节（DRG）的感觉神经元和神经胶质细胞。为了鉴定影响神经嵴细胞命运特化的基因，我们在斑马鱼中进行了正向遗传筛选，以寻找导致 DRG 缺陷的突变。该筛选产生了一个缺乏所有 DRG 的突变体，我们将其命名为感觉剥夺（sensory deprived，sdp）。我们总共鉴定了 sdp 的四个等位基因，它们都在编码富含半胱氨酸的 Kazal 基序的回复诱导蛋白（reversion-inducing cysteine-rich protein containing Kazal motifs，Reck）的基因中存在损伤。Reck 是一种金属蛋白酶抑制剂，先前已证明其可调节细胞运动。我们发现 reck 的功能不仅对 DRG 形成是必需的，而且足以挽救 sdp 表型。reck 在神经嵴细胞中表达，并以细胞自主的方式对适当的感觉神经元形成是必需的。在 reck 功能缺失的情况下，感觉神经元前体不能迁移到 DRG 的位置，这表明该分子对于正确的迁移和分化至关重要。
