Caric D, Raphael H, Viti J, Feathers A, Wancio D, Lillien L
Department of Neurobiology and Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, W1454 Biomedical Science Tower, Pittsburgh, PA 15261, USA.
Development. 2001 Nov;128(21):4203-16. doi: 10.1242/dev.128.21.4203.
Epidermal growth factor receptors (EGFRs) have been implicated in the control of migration in the telencephalon, but the mechanism underlying their contribution is unclear. We show that expression of a threshold level of EGFRs confers chemotactic competence in stem cells, neurons and astrocytes in cortical explants. This level of receptor expression is normally achieved by a subpopulation of cells during mid-embryonic development. Cells that express high levels of EGFR are located in migration pathways, including the tangential pathway to the olfactory bulb via the rostral migratory stream (RMS), the lateral cortical stream (LCS) leading to ventrolateral cortex and the radial pathway from proliferative zones to cortical plate. The targets of these pathways express the ligands HB-EGF and/or TGFalpha. To test the idea that EGFRs mediate chemotactic migration these pathways, we increased the size of the population of cells expressing threshold levels of EGFRs in vivo by viral transduction. Our results suggest that EGFRs mediate migration radially to the cortical plate and ventrolaterally in the LCS, but not tangentially in the RMS. Within the bulb, however, EGFRs also mediate radial migration. Our findings suggest that developmental changes in EGFR expression, together with changes in ligand expression regulate the migration of specific populations of cells in the telencephalon by a chemoattractive mechanism.
表皮生长因子受体（EGFRs）已被证实参与端脑迁移的调控，但其作用机制尚不清楚。我们发现，EGFRs表达达到阈值水平可赋予皮质外植体中的干细胞、神经元和星形胶质细胞趋化能力。在胚胎中期发育过程中，通常有一部分细胞能达到这种受体表达水平。高表达EGFR的细胞位于迁移路径中，包括通过吻侧迁移流（RMS）向嗅球的切线路径、通向腹外侧皮质的外侧皮质流（LCS）以及从增殖区到皮质板的径向路径。这些路径的靶标表达配体HB-EGF和/或TGFα。为了验证EGFRs介导这些路径趋化迁移的观点，我们通过病毒转导在体内增加了表达EGFR阈值水平的细胞群体数量。我们的结果表明，EGFRs介导细胞径向迁移至皮质板以及在LCS中向腹外侧迁移，但不介导在RMS中的切线迁移。然而，在嗅球内，EGFRs也介导径向迁移。我们的研究结果表明，EGFR表达的发育变化以及配体表达的变化通过趋化吸引机制调节端脑中特定细胞群体的迁移。
