Atypical cadherins Celsr1-3 differentially regulate migration of facial branchiomotor neurons in mice.
Atypical cadherins Celsr1-3 differentially regulate migration of facial branchiomotor neurons in mice.
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DOI：
10.1523/jneurosci.0124-10.2010
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发表时间：
2010-07-14
期刊：
影响因子：
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通讯作者：
Tissir F
中科院分区：
文献类型：
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作者：
Qu Y;Glasco DM;Zhou L;Sawant A;Ravni A;Fritzsch B;Damrau C;Murdoch JN;Evans S;Pfaff SL;Formstone C;Goffinet AM;Chandrasekhar A;Tissir F
在后脑发育过程中，面鳃神经元（FBM神经元）从内侧菱形节（r）4迁移到外侧r6。在斑马鱼中，平面细胞极性基因celsr 2和frizzled 3a的突变阻断了FBM神经元的尾部迁移。在这里，我们研究了钙粘蛋白Celsr 1 -3和Fzd 3在小鼠FBM神经元迁移中的作用。在Celsr 1突变体（敲除和Crash等位基因）中，尾侧迁移受到损害，神经元经常迁移到r2和r3，以及横向。这些表型不是由后脑模式或神经元特异性缺陷引起的。Celsr 1在FBM神经元前体和底板中表达，但在FBM神经元中不表达。与此一致，条件性失活表明Celsr 1在FBM神经元迁移中的功能是非细胞自主的。在Celsr 2突变体中，FBM神经元开始向尾部迁移，但过早地迁移到外侧R4和R5。这种表型通过FBM神经元中Celsr 3的失活而增强，并通过Fzd 3的失活而模拟。此外，Celsr 2对Celsr 1具有上位性。这些数据表明，Celsr 1 -3差异调节FBM神经元迁移。Celsr 1有助于指定FBM神经元迁移的方向，而Celsr 2和3控制其迁移的能力。
During hindbrain development, facial branchiomotor neurons (FBM neurons) migrate from medial rhombomere (r) 4 to lateral r6. In zebrafish, mutations in planar cell polarity genes celsr2 and frizzled3a block caudal migration of FBM neurons. Here, we investigated the role of cadherins Celsr1-3, and Fzd3 in FBM neuron migration in mice. In Celsr1 mutants (knock-out and Crash alleles), caudal migration was compromised and neurons often migrated rostrally into r2 and r3, as well as laterally. These phenotypes were not caused by defects in hindbrain patterning or neuronal specification. Celsr1 is expressed in FBM neuron precursors and the floor plate, but not in FBM neurons. Consistent with this, conditional inactivation showed that the function of Celsr1 in FBM neuron migration was non-cell autonomous. In Celsr2 mutants, FBM neurons initiated caudal migration but moved prematurely into lateral r4 and r5. This phenotype was enhanced by inactivation of Celsr3 in FBM neurons and mimicked by inactivation of Fzd3. Furthermore, Celsr2 was epistatic to Celsr1. These data indicate that Celsr1-3 differentially regulate FBM neuron migration. Celsr1 helps to specify the direction of FBM neuron migration, whereas Celsr2 and 3 control its ability to migrate.