增强WNT信号通路可恢复Tbr1突变体中皮质神经元棘突成熟和突触形成。
Enhancing WNT Signaling Restores Cortical Neuronal Spine Maturation and Synaptogenesis in Tbr1 Mutants.
作者信息
Fazel Darbandi Siavash, Robinson Schwartz Sarah E, Pai Emily Ling-Lin, Everitt Amanda, Turner Marc L, Cheyette Benjamin N R, Willsey A Jeremy, State Matthew W, Sohal Vikaas S, Rubenstein John L R
机构信息
Department of Psychiatry and UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
出版信息
Cell Rep. 2020 Apr 14;31(2):107495. doi: 10.1016/j.celrep.2020.03.059.
Tbr1 is a high-confidence autism spectrum disorder (ASD) gene encoding a transcription factor with distinct pre- and postnatal functions. Postnatally, Tbr1 conditional knockout (CKO) mutants and constitutive heterozygotes have immature dendritic spines and reduced synaptic density. Tbr1 regulates expression of several genes that underlie synaptic defects, including a kinesin (Kif1a) and a WNT-signaling ligand (Wnt7b). Furthermore, Tbr1 mutant corticothalamic neurons have reduced thalamic axonal arborization. LiCl and a GSK3β inhibitor, two WNT-signaling agonists, robustly rescue the dendritic spines and the synaptic and axonal defects, suggesting that this could have relevance for therapeutic approaches in some forms of ASD.
Tbr1是一个高可信度的自闭症谱系障碍（ASD）基因，编码一种具有不同产前和产后功能的转录因子。出生后，Tbr1条件性敲除（CKO）突变体和组成型杂合子具有未成熟的树突棘，突触密度降低。Tbr1调节多个导致突触缺陷的基因的表达，包括一种驱动蛋白（Kif1a）和一种WNT信号配体（Wnt7b）。此外，Tbr1突变的皮质丘脑神经元丘脑轴突分支减少。氯化锂和一种GSK3β抑制剂这两种WNT信号激动剂，能有力地挽救树突棘以及突触和轴突缺陷，这表明这可能与某些形式的ASD的治疗方法相关。
Zotero 插件