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MET 受体酪氨酸激酶在中前额叶和视皮质发育过程中的亚类特异性表达模式。

Subclass-specific expression patterns of MET receptor tyrosine kinase during development in medial prefrontal and visual cortices.

机构信息

Program in Developmental Neuroscience and Neurogenetics, Children's Hospital Los Angeles, The Saban Research Institute, Los Angeles, California, USA.

Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

出版信息

J Comp Neurol. 2023 Jan;531(1):132-148. doi: 10.1002/cne.25418. Epub 2022 Oct 6.

Abstract

Met encodes a receptor tyrosine kinase (MET) that is expressed during development and regulates cortical synapse maturation. Conditional deletion of Met in the nervous system during embryonic development leads to deficits in adult contextual fear learning, a medial prefrontal cortex (mPFC)-dependent cognitive task. MET also regulates the timing of critical period plasticity for ocular dominance in primary visual cortex (V1). However, the underlying circuitry responsible remains unknown. Therefore, this study determines the broad expression patterns of MET throughout postnatal development in mPFC and V1 projection neurons (PNs), providing insight into similarities and differences in the neuronal subtypes and temporal patterns of MET expression between cortical areas. Using a transgenic mouse line that expresses green fluorescent protein (GFP) in Met neurons, immunofluorescence and confocal microscopy were performed to visualize MET-GFP cell bodies and PN subclass-specific protein markers. Analyses reveal that the MET expression is highly enriched in infragranular layers of mPFC, but in supragranular layers of V1. Interestingly, temporal regulation of the percentage of MET neurons across development not only differs between cortical regions but also is distinct between lamina within a cortical region. Further, MET is expressed predominantly in the subcerebral PN subclass in mPFC, but the intratelencephalic PN subclass in V1. The data suggest that MET signaling influences the development of distinct circuits in mPFC and V1 that underlie subcerebral and intracortical functional deficits following Met deletion, respectively.

摘要

Met 编码一种受体酪氨酸激酶 (MET),它在发育过程中表达,并调节皮质突触成熟。在胚胎发育过程中,神经系统中条件性缺失 Met 会导致成年上下文恐惧学习缺陷,这是一种内侧前额叶皮层 (mPFC) 依赖的认知任务。MET 还调节初级视觉皮层 (V1) 中眼优势的关键期可塑性的时间。然而,负责的潜在电路仍然未知。因此,本研究确定了 MET 在 mPFC 和 V1 投射神经元 (PN) 中的广泛表达模式,为皮质区域之间神经元亚型和 MET 表达的时间模式的相似性和差异性提供了深入了解。使用一种在 Met 神经元中表达绿色荧光蛋白 (GFP) 的转基因小鼠系,通过免疫荧光和共聚焦显微镜观察 MET-GFP 细胞体和 PN 亚类特异性蛋白标记物。分析表明,MET 表达在 mPFC 的颗粒下层高度富集,但在 V1 的颗粒上层富集。有趣的是,MET 神经元百分比的时间调节不仅在皮质区域之间存在差异,而且在皮质区域内的层之间也存在差异。此外,MET 在 mPFC 中的 subcerebral PN 亚类中表达占主导地位,但在 V1 的 intratelencephalic PN 亚类中表达占主导地位。数据表明,MET 信号影响 mPFC 和 V1 中不同回路的发育,分别导致 Met 缺失后 subcerebral 和 intracortical 功能缺陷。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6043/9827848/7dca956b365d/CNE-531-132-g003.jpg

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