Cadherins mediate sequential roles through a hierarchy of mechanisms in the developing mammillary body.
Cadherins mediate sequential roles through a hierarchy of mechanisms in the developing mammillary body.
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DOI：
10.3389/fnana.2015.00029
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发表时间：
2015
影响因子：
2.9
通讯作者：
Alvarez-Bolado G
中科院分区：
文献类型：
--
作者：
Szabó NE;Haddad-Tóvolli R;Zhou X;Alvarez-Bolado G
钙粘蛋白（粘附膜蛋白家族）复杂组合的表达在发育中的中枢神经系统中很常见。在此基础上，组合钙粘蛋白编码长期以来一直被认为是神经元分类的基础，并最终负责大脑的层，列和核。然而，钙粘蛋白的这种特殊功能的实验证据已被证明难以获得，问题仍然不清楚。或者，非特异性的，非组合的，纯粹定量的粘附差异已被提出来解释大脑中的神经元排序。钙粘蛋白的结合是脑细胞结构的基础吗？我们使用一个定义明确的前脑核--乳头体（MBO）作为模型来探讨这个问题，它显示出一种单一的钙粘蛋白（Cdh 11）的强烈、均匀的表达和Cdh 6、Cdh-8和Cdh-10的模式化、组合表达。我们发现，除了已知的组合Cdh模式，MBO细胞被组织成第二个，非重叠的模式分组神经元与神经发生的相同日期。我们报告说，在Foxb 1小鼠突变体，Cdh 11的表达未能维持在MBO的发展。这破坏了突变MBO中基于组合和基于出生日期的排序。在子宫内的RNA干扰（RNAi）实验敲低Cdh 11在MBO-命运的迁移神经元在一个特定的年龄表明，Cdh 11的表达所需的时间顺序入口的MBO。我们的研究结果表明，在发展中的MBO的神经元排序是由基于粘附的，非组合的机制，保持神经元根据出生日期信息排序（可能匹配它们的目标神经元按时间顺序排序以相同的方式）。非特异性粘附机制也会阻止钙粘蛋白组合改变基于出生日期的分选。钙粘蛋白组合可能会晚些时候通过特定的轴突成束和最终的靶点识别来支持特定的突触发生。
Expression of intricate combinations of cadherins (a family of adhesive membrane proteins) is common in the developing central nervous system. On this basis, a combinatorial cadherin code has long been proposed to underlie neuronal sorting and to be ultimately responsible for the layers, columns and nuclei of the brain. However, experimental proof of this particular function of cadherins has proven difficult to obtain and the question is still not clear. Alternatively, non-specific, non-combinatorial, purely quantitative adhesive differentials have been proposed to explain neuronal sorting in the brain. Do cadherin combinations underlie brain cytoarchitecture? We approached this question using as model a well-defined forebrain nucleus, the mammillary body (MBO), which shows strong, homogeneous expression of one single cadherin (Cdh11) and patterned, combinatorial expression of Cdh6, −8 and −10. We found that, besides the known combinatorial Cdh pattern, MBO cells are organized into a second, non-overlapping pattern grouping neurons with the same date of neurogenesis. We report that, in the Foxb1 mouse mutant, Cdh11 expression fails to be maintained during MBO development. This disrupted the combination-based as well as the birthdate-based sorting in the mutant MBO. In utero RNA interference (RNAi) experiments knocking down Cdh11 in MBO-fated migrating neurons at one specific age showed that Cdh11 expression is required for chronological entrance in the MBO. Our results suggest that neuronal sorting in the developing MBO is caused by adhesion-based, non-combinatorial mechanisms that keep neurons sorted according to birthdate information (possibly matching them to target neurons chronologically sorted in the same manner). Non-specific adhesion mechanisms would also prevent cadherin combinations from altering the birthdate-based sorting. Cadherin combinations would presumably act later to support specific synaptogenesis through specific axonal fasciculation and final target recognition.
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影响因子：
16.2
作者：
Elia, Lisa P.;Yamamoto, Miya;Reichardt, Louis F.
通讯作者：
Reichardt, Louis F.
影响因子：
1.2
作者：
Haddad-Tvolli, Roberta;Szabo, Nora-Emke;Alvarez-Bolado, Gonzalo
通讯作者：
Alvarez-Bolado, Gonzalo
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
8.4
作者：
Habashy, Hany Onsy;Powe, Desmond G.;Ellis, Ian O.
通讯作者：
Ellis, Ian O.
DOI：
10.1093/bfgp/elm008
发表时间：
2007-06-01
期刊：
Briefings in Functional Genomics & Proteomics
影响因子：
--
作者：
Barbaric, Ivana;Miller, Gaynor;Dear, T. Neil
通讯作者：
Dear, T. Neil