The atypical cadherin Celsr1 functions non-cell autonomously to block rostral migration of facial branchiomotor neurons in mice.

The atypical cadherin Celsr1 functions non-cell autonomously to block rostral migration of facial branchiomotor neurons in mice.
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DOI:
10.1016/j.ydbio.2016.07.004
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发表时间:
2016-09-01
影响因子:
2.7
通讯作者:
Chandrasekhar, Anand
Chandrasekhar, Anand
中科院分区:
生物学3区
文献类型:
--
作者:
Glasco, Derrick M.;Pike, Whitney;Qu, Yibo;Reustle, Lindsay;Misra, Kamana;Di Bonito, Maria;Studer, Michele;Fritzsch, Bernd;Goffinet, Andre M.;Tissir, Fadel;Chandrasekhar, Anand

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面鳃神经元从r4向r6的尾侧迁移是研究神经元迁移机制的一个很好的模型。虽然几个Wnt/平面细胞极性(PCP)组件所需的FBM神经元迁移,只有Celsr 1,一种非典型的钙粘蛋白,调节小鼠的迁移方向。在Celsr 1突变体中,FBM神经元的一个子集向吻侧而不是向尾侧迁移。有趣的是,Celsr 1在迁移的FBM神经元中不表达,而是在相邻的底板和相邻的心室区中表达。为了评估不同表达域对神经元迁移的贡献,我们在特定细胞类型中有条件地失活Celsr 1。有趣的是,Celsr 1在r3-r5脑室区的失活,而不是在底板,导致FBM神经元的吻侧迁移,非常类似Celsr 1突变体的迁移缺陷。染料填充实验表明,在Celsr 1突变体的喙迁移FBM神经元起源于前缘的r4。这些数据强烈表明,Celsr 1通过抑制可以吸引FBM神经元的吻侧后脑中的分子线索来确保FBM神经元向尾侧迁移。
The caudal migration of facial branchiomotor (FBM) neurons from rhombomere (r) 4 to r6 in the hindbrain is an excellent model to study neuronal migration mechanisms. Although several Wnt/Planar Cell Polarity (PCP) components are required for FBM neuron migration, only Celsr1, an atypical cadherin, regulates the direction of migration in mice. In Celsr1 mutants, a subset of FBM neurons migrates rostrally instead of caudally. Interestingly, Celsr1 is not expressed in the migrating FBM neurons, but rather in the adjacent floor plate and adjoining ventricular zone. To evaluate the contribution of different expression domains to neuronal migration, we conditionally inactivated Celsr1 in specific cell types. Intriguingly, inactivation of Celsr1 in the ventricular zone of r3-r5, but not in the floor plate, leads to rostral migration of FBM neurons, greatly resembling the migration defect of Celsr1 mutants. Dye fill experiments indicate that the rostrally-migrated FBM neurons in Celsr1 mutants originate from the anterior margin of r4. These data suggest strongly that Celsr1 ensures that FBM neurons migrate caudally by suppressing molecular cues in the rostral hindbrain that can attract FBM neurons.
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