Budi Erine H, Patterson Larissa B, Parichy David M
Department of Biology, Institute for Stem Cell and Regenerative Medicine, University of Washington,Seattle, WA 98195-1800, USA.
Development. 2008 Aug;135(15):2603-14. doi: 10.1242/dev.019299. Epub 2008 May 28.
Vertebrate pigment cells are derived from neural crest cells and are a useful system for studying neural crest-derived traits during post-embryonic development. In zebrafish, neural crest-derived melanophores differentiate during embryogenesis to produce stripes in the early larva. Dramatic changes to the pigment pattern occur subsequently during the larva-to-adult transformation, or metamorphosis. At this time, embryonic melanophores are replaced by newly differentiating metamorphic melanophores that form the adult stripes. Mutants with normal embryonic/early larval pigment patterns but defective adult patterns identify factors required uniquely to establish, maintain or recruit the latent precursors to metamorphic melanophores. We show that one such mutant, picasso, lacks most metamorphic melanophores and results from mutations in the ErbB gene erbb3b, which encodes an EGFR-like receptor tyrosine kinase. To identify critical periods for ErbB activities, we treated fish with pharmacological ErbB inhibitors and also knocked down erbb3b by morpholino injection. These analyses reveal an embryonic critical period for ErbB signaling in promoting later pigment pattern metamorphosis, despite the normal patterning of embryonic/early larval melanophores. We further demonstrate a peak requirement during neural crest migration that correlates with early defects in neural crest pathfinding and peripheral ganglion formation. Finally, we show that erbb3b activities are both autonomous and non-autonomous to the metamorphic melanophore lineage. These data identify a very early, embryonic, requirement for erbb3b in the development of much later metamorphic melanophores, and suggest complex modes by which ErbB signals promote adult pigment pattern development.
脊椎动物色素细胞起源于神经嵴细胞，是研究胚胎后发育过程中神经嵴衍生特征的有用系统。在斑马鱼中，神经嵴衍生的黑素细胞在胚胎发育过程中分化，在早期幼体中形成条纹。随后在幼体到成体的转变或变态过程中，色素模式发生显著变化。此时，胚胎黑素细胞被新分化的变态黑素细胞取代，后者形成成体条纹。具有正常胚胎/早期幼体色素模式但成体模式有缺陷的突变体可鉴定出建立、维持或招募变态黑素细胞潜在前体所需的独特因子。我们发现一个这样的突变体——毕加索，缺少大多数变态黑素细胞，它是由编码类表皮生长因子受体酪氨酸激酶的ErbB基因erbb3b发生突变所致。为了确定ErbB活性的关键时期，我们用ErbB药理抑制剂处理鱼类，并通过吗啉代注射敲低erbb3b。这些分析揭示了ErbB信号传导在促进后期色素模式变态方面的一个胚胎关键时期，尽管胚胎/早期幼体黑素细胞的模式正常。我们进一步证明在神经嵴迁移期间存在一个需求高峰，这与神经嵴路径寻找和外周神经节形成的早期缺陷相关。最后，我们表明erbb3b活性对变态黑素细胞谱系既是自主的又是非自主的。这些数据确定了在后期变态黑素细胞发育过程中对erbb3b非常早期的胚胎需求，并提示了ErbB信号促进成体色素模式发育的复杂模式。
