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Cranial neural crest cell migration in the avian embryo and the roles of Eph-A4 and ephrin-A5.

机译:颅神经neural细胞在禽胚胎中的迁移以及Eph-A4和ephrin-A5的作用。

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摘要

The neural crest is a transient population of cells that migrate away from the dorsal neural tube in the vertebrate embryo. As the developing hindbrain constricts into rhombomeres, cranial neural crest cells migrate in three discrete streams adjacent to even-numbered rhombomeres, rhombomere 2 (r2), r4, and r6.; To test the role of intrinsic versus extrinsic cues in influencing an individual cell's trajectory, we implanted physical barriers in the chick mesoderm, distal to emerging neural crest cells (NCCs). We analyzed spatio-temporal dynamics as NCCs encountered and responded to the barriers by using time-lapse confocal microscopy and cell tracking analysis. The majority of NCCs were able to overcome physical barriers. Even though the lead cells become temporarily blocked by a barrier, follower cells find a novel pathway around a barrier and become de novo leaders of a new stream. Quantitative analyses of cell trajectories find cells that encounter an r3 barrier migrate significantly faster but less directly than cells that encounter an r4 barrier, which migrate normally. NCCs can also migrate into normally repulsive territory as they reroute. These results suggest that cranial neural crest cell trajectories are not intrinsically determined. NCCs can respond to minor alterations in the environment to retarget a peripheral destination. Both intrinsic and extrinsic cues are important in patterning.; We then tested the role of Eph/ephrin signaling on cranial neural crest migration by ectopically expressing full-length ephrin-A5 ligand; a truncated, constitutively active EphA4 receptor; and a truncated, kinase-dead EphA4 receptor within migratory neural crest cells. Ectopic expression of ephrin-A5 specifically causes the r6 subpopulation of neural crest cells to have truncated migration but does not affect directionality, suggesting that the r6 neural crest cells properly follow guidance cues. Our results support a role for ephrin-A5 in regulating the extent of migration.; Ectopic expression of constitutively active, truncated EphA4 causes NCCs to migrate aberrantly around the otic vesicle. Pathfinding errors are accompanied by changes in migratory behavior, with the NCCs migrating faster but with less directionality. Expression of a truncated, kinase-dead version of EphA4 also leads to pathfinding errors. Our results suggest Eph activity is involved in guidance and extent of migration.
机译:神经c是从脊椎动物胚胎的背神经管迁移出来的瞬时细胞群。随着发育中的后脑收缩成菱形,颅神经rest细胞在与偶数菱形,菱形2(r2),r4和r6相邻的三个离散流中迁移。为了测试内在线索与外在线索在影响单个细胞轨迹中的作用,我们在雏鸡中胚层中向新兴神经barrier细胞(NCC)的远端植入了物理屏障。我们通过使用时移共聚焦显微镜和细胞跟踪分析,分析了NCC遇到并响应障碍时的时空动态。大多数NCC能够克服物理障碍。即使前导细胞暂时被屏障阻滞,跟随细胞仍会在屏障周围找到新的途径,并成为新流的从头开始。对细胞轨迹的定量分析发现,遇到r3障碍的细胞迁移速度明显快于但比遇到r4障碍的细胞迁移速度要快,后者通常会迁移。 NCC在重新路由时也可以迁移到通常排斥的区域。这些结果表明,颅神经neural细胞的轨迹不是固有地确定的。 NCC可以对环境中的细微变化做出响应,以重新定位外围目标。内在线索和外在线索都对图案化很重要。然后,我们通过异位表达全长ephrin-A5配体来测试Eph / ephrin信号在颅神经c迁移中的作用;截短的组成型活性EphA4受体;以及在迁徙的神经rest细胞中的一个激酶死亡的截短的EphA4受体。 ephrin-A5的异位表达特异性地导致神经cells细胞的r6亚群具有截短的迁移,但不影响方向性,表明r6神经c细胞正确地遵循了指导线索。我们的结果支持ephrin-A5在调节迁移程度中的作用。组成性活性,截短的EphA4的异位表达导致NCC在耳囊周围异常迁移。寻路错误伴随着迁徙行为的变化,NCC迁移速度更快,但方向性更差。截短的,激酶死亡的EphA4版本的表达也会导致寻路错误。我们的结果表明,Eph活性与迁移的指导和程度有关。

著录项

  • 作者

    Lu, Carole Chih-Chen.;

  • 作者单位

    California Institute of Technology.;

  • 授予单位 California Institute of Technology.;
  • 学科 Biology Cell.; Biology Animal Physiology.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 117 p.
  • 总页数 117
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;生理学;
  • 关键词

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