Reduced mTORC1-signaling in progenitor cells leads to retinal lamination deficits

IF 2 3区 生物学 Q2 ANATOMY & MORPHOLOGY Developmental Dynamics Pub Date : 2024-03-28 DOI:10.1002/dvdy.707
Christoffer Nord, Iwan Jones, Maria Garcia-Maestre, Anna-Carin Hägglund, Leif Carlsson
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Abstract

Background

Neuronal lamination is a hallmark of the mammalian central nervous system (CNS) and underlies connectivity and function. Initial formation of this tissue architecture involves the integration of various signaling pathways that regulate the differentiation and migration of neural progenitor cells.

Results

Here, we demonstrate that mTORC1 mediates critical roles during neuronal lamination using the mouse retina as a model system. Down-regulation of mTORC1-signaling in retinal progenitor cells by conditional deletion of Rptor led to decreases in proliferation and increased apoptosis during embryogenesis. These developmental deficits preceded aberrant lamination in adult animals which was best exemplified by the fusion of the outer and inner nuclear layer and the absence of an outer plexiform layer. Moreover, ganglion cell axons originating from each Rptor-ablated retina appeared to segregate to an equal degree at the optic chiasm with both contralateral and ipsilateral projections displaying overlapping termination topographies within several retinorecipient nuclei. In combination, these visual pathway defects led to visually mediated behavioral deficits.

Conclusions

This study establishes a critical role for mTORC1-signaling during retinal lamination and demonstrates that this pathway regulates diverse developmental mechanisms involved in driving the stratified arrangement of neurons during CNS development.

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祖细胞中的 mTORC1 信号减少会导致视网膜分层缺陷。
背景:神经元分层是哺乳动物中枢神经系统(CNS)的标志,是连接和功能的基础。这种组织结构的最初形成涉及到调节神经祖细胞分化和迁移的各种信号通路的整合:结果:在这里,我们以小鼠视网膜为模型系统,证明了 mTORC1 在神经元分层过程中的关键作用。通过条件性缺失 Rptor 下调视网膜祖细胞中的 mTORC1 信号导致胚胎发育过程中增殖减少和凋亡增加。这些发育缺陷导致成年动物的视网膜分层出现异常,最典型的表现是核外层和核内层的融合以及外层丛状层的缺失。此外,神经节细胞轴突起源于每个被 Rptor 削弱的视网膜,它们在视交叉处的分离程度似乎相同,对侧和同侧的投射在几个视网膜感受核内显示出重叠的终止拓扑。这些视觉通路缺陷共同导致了视觉介导的行为障碍:这项研究确定了 mTORC1 信号在视网膜分层过程中的关键作用,并证明该通路调节了中枢神经系统发育过程中神经元分层排列的多种发育机制。
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来源期刊
Developmental Dynamics
Developmental Dynamics 生物-发育生物学
CiteScore
5.10
自引率
8.00%
发文量
116
审稿时长
3-8 weeks
期刊介绍: Developmental Dynamics, is an official publication of the American Association for Anatomy. This peer reviewed journal provides an international forum for publishing novel discoveries, using any model system, that advances our understanding of development, morphology, form and function, evolution, disease, stem cells, repair and regeneration.
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