Homophilic binding of the neural cell adhesion molecule CHL1 regulates development of ventral midbrain dopaminergic pathways.
Homophilic binding of the neural cell adhesion molecule CHL1 regulates development of ventral midbrain dopaminergic pathways.
复制标题
神经细胞粘附分子CHL1的同质结合调节腹中脑多巴胺能途径的发展。
DOI：
10.1038/s41598-017-09599-y
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发表时间：
2017-08-24
影响因子：
4.6
通讯作者：
Parish CL
中科院分区：
文献类型：
--
作者：
Alsanie WF;Penna V;Schachner M;Thompson LH;Parish CL
腹侧中脑（VM）多巴胺能（DA）通路的异常发育，对运动和认知功能至关重要，可能是许多神经系统疾病的基础，从而突出了理解相关神经元的诞生和连接的重要性。虽然一些监管机构的VM DA神经发生是已知的，过程中涉及的后期发展的事件，包括终端分化和轴突形态发生，是不太清楚。最近的转录分析研究开发VM确定在这些阶段中表达的基因，包括细胞粘附分子与同源性L1（Chl 1）。在这里，我们映射的时间和空间表达的CHL 1和评估功能的作用，基质结合和可溶性形式的蛋白质在VM DA的发展。结果显示，VM中的早期CHL 1，与DA祖细胞迁移和分化中的作用相对应。随后，我们证明了CHL 1在轴突延伸和排斥中的作用，选择性地对DA神经元，提示在引导前脑靶点和远离后脑核中的作用。在某种程度上，CHL 1通过嗜同性CHL 1-CHL 1相互作用介导这些作用。总的来说，这些发现增强了我们对VM DA途径发展的认识，并可能为理解DA发育条件如自闭症谱系障碍提供新的见解。
Abnormal development of ventral midbrain (VM) dopaminergic (DA) pathways, essential for motor and cognitive function, may underpin a number of neurological disorders and thereby highlight the importance of understanding the birth and connectivity of the associated neurons. While a number of regulators of VM DA neurogenesis are known, processes involved in later developmental events, including terminal differentiation and axon morphogenesis, are less well understood. Recent transcriptional analysis studies of the developing VM identified genes expressed during these stages, including the cell adhesion molecule with homology to L1 (Chl1). Here, we map the temporal and spatial expression of CHL1 and assess functional roles of substrate-bound and soluble-forms of the protein during VM DA development. Results showed early CHL1 in the VM, corresponding with roles in DA progenitor migration and differentiation. Subsequently, we demonstrated roles for CHL1 in both axonal extension and repulsion, selectively of DA neurons, suggestive of a role in guidance towards forebrain targets and away from hindbrain nuclei. In part, CHL1 mediates these roles through homophilic CHL1-CHL1 interactions. Collectively, these findings enhance our knowledge of VM DA pathways development, and may provide new insights into understanding DA developmental conditions such as autism spectrum disorders.
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DOI：
10.1016/s0165-3806(00)00129-2
发表时间：
2001-01-31
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Demyanenko, GP;Shibata, Y;Maness, PF
通讯作者：
Maness, PF
影响因子：
3.5
作者：
Huang, Xin;Zhu, Ling-ling;Fan, Ming
通讯作者：
Fan, Ming
影响因子：
5.3
作者：
Jakovcevski, Igor;Wu, Junfang;Schachner, Melitta
通讯作者：
Schachner, Melitta
影响因子：
2.1
作者：
Morag, Ayelet;Pasmanik-Chor, Metsada;Gurwitz, David
通讯作者：
Gurwitz, David
影响因子：
3
作者：
Parish, Clare L.;Arenas, Ernest
通讯作者：
Arenas, Ernest