A dual-strategy expression screen for candidate connectivity labels in the developing thalamus.
A dual-strategy expression screen for candidate connectivity labels in the developing thalamus.
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DOI：
10.1371/journal.pone.0177977
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Mitchell KJ
中科院分区：
文献类型：
--
作者：
Bibollet-Bahena O;Okafuji T;Hokamp K;Tear G;Mitchell KJ
丘脑或大脑的“内腔”被分成约30个离散的核，具有高度特定的传入和传出连接模式。为了确定可能指导这些连接模式的基因，我们使用了两种策略。首先，我们使用生物信息学管道来调查线虫、果蝇、小鼠和人类的预测蛋白质组，以寻找在已知的引导或连接分子中发现的含有任何基序的细胞外蛋白。其次，我们对Allen发育中的小鼠脑图谱数据进行聚类分析，以确定编码表面蛋白的基因，这些表面蛋白的表达与已知的引导或连接分子的时间谱相似。在这两种情况下，我们随后筛选了在发育中的丘脑中选择性表达模式的结果基因。这些方法在发育中的丘脑中确定了82个候选连接标签。这些分子包括Ephrin、ephf受体、cadherin、原cadherin、semaphorin、plexin、Odz/teneurin、Neto、cerebellin、calsyntenin和Netrin-G家族的许多成员，以及免疫球蛋白（Ig）和富亮氨酸受体（LRR）超家族的各种成员、酪氨酸激酶和磷酸酶受体、各种生长因子和受体。以及大量与轴突引导或神经元连接无关的各种膜相关或分泌蛋白。它们表达模式的多样性表明，丘脑核彼此之间高度分化，每个核都显示出这些分子的独特曲目，与丘脑连接规范的组合逻辑一致。
The thalamus or “inner chamber” of the brain is divided into ~30 discrete nuclei, with highly specific patterns of afferent and efferent connectivity. To identify genes that may direct these patterns of connectivity, we used two strategies. First, we used a bioinformatics pipeline to survey the predicted proteomes of nematode, fruitfly, mouse and human for extracellular proteins containing any of a list of motifs found in known guidance or connectivity molecules. Second, we performed clustering analyses on the Allen Developing Mouse Brain Atlas data to identify genes encoding surface proteins expressed with temporal profiles similar to known guidance or connectivity molecules. In both cases, we then screened the resultant genes for selective expression patterns in the developing thalamus. These approaches identified 82 candidate connectivity labels in the developing thalamus. These molecules include many members of the Ephrin, Eph-receptor, cadherin, protocadherin, semaphorin, plexin, Odz/teneurin, Neto, cerebellin, calsyntenin and Netrin-G families, as well as diverse members of the immunoglobulin (Ig) and leucine-rich receptor (LRR) superfamilies, receptor tyrosine kinases and phosphatases, a variety of growth factors and receptors, and a large number of miscellaneous membrane-associated or secreted proteins not previously implicated in axonal guidance or neuronal connectivity. The diversity of their expression patterns indicates that thalamic nuclei are highly differentiated from each other, with each one displaying a unique repertoire of these molecules, consistent with a combinatorial logic to the specification of thalamic connectivity.