Essential role for PDGF signaling in ophthalmic trigeminal placode induction
Essential role for PDGF signaling in ophthalmic trigeminal placode induction
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DOI：
10.1242/dev.017954
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发表时间：
2008-05-15
期刊：
影响因子：
4.6
通讯作者：
Bronner-Fraser, Marianne
中科院分区：
文献类型：
--
作者：
McCabe, Kathryn L.;Bronner-Fraser, Marianne
头部的大部分周围神经系统来自外胚层增厚，称为基板，其分层或内陷形成颅神经节和感觉器官。三叉神经节位于中脑外侧，通过神经管和相邻外胚层之间的相互作用形成。这种诱导触发Pax3的表达、基板细胞的侵入以及它们向神经元的分化。然而，潜在信号的分子性质仍然未知。在这里，我们调查的作用，PDGF信号在眼三叉神经基板诱导。通过原位杂交，PDGF受体β在三叉神经基板形成时在颅外胚层中表达，配体PDGFD在中脑神经褶皱中表达。在体外阻断PDGF信号导致剂量依赖性地废除鹌鹑外胚层与鸡神经管的重组体中的Pax3表达，其重演基板诱导。卵内微量注射PDGF抑制剂可导致Pax3以及后来的基板标记物CD 151的类似损失，以及神经元分化的失败。相反，微量注射外源性PDGFD增加三叉神经基板中的Pax3+细胞和冷凝神经节中的神经元的数量。我们的研究结果提供了第一个证据，参与眼（opV）三叉神经基板诱导的信号通路。
Much of the peripheral nervous system of the head is derived from ectodermal thickenings, called placodes, that delaminate or invaginate to form cranial ganglia and sense organs. The trigeminal ganglion, which arises lateral to the midbrain, forms via interactions between the neural tube and adjacent ectoderm. This induction triggers expression of Pax3, ingression of placode cells and their differentiation into neurons. However, the molecular nature of the underlying signals remains unknown. Here, we investigate the role of PDGF signaling in ophthalmic trigeminal placode induction. By in situ hybridization, PDGF receptor beta is expressed in the cranial ectoderm at the time of trigeminal placode formation, with the ligand PDGFD expressed in the midbrain neural folds. Blocking PDGF signaling in vitro results in a dose-dependent abrogation of Pax3 expression in recombinants of quail ectoderm with chick neural tube that recapitulate placode induction. In ovo microinjection of PDGF inhibitor causes a similar loss of Pax3 as well as the later placodal marker, CD151, and failure of neuronal differentiation. Conversely, microinjection of exogenous PDGFD increases the number of Pax3+ cells in the trigeminal placode and neurons in the condensing ganglia. Our results provide the first evidence for a signaling pathway involved in ophthalmic (opV) trigeminal placode induction.