High-throughput three-dimensional chemotactic assays reveal steepness-dependent complexity in neuronal sensation to molecular gradients

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review

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Detail(s)

Original languageEnglish
Article number4745
Journal / PublicationNature Communications
Volume9
Publication statusPublished - 12 Nov 2018

Link(s)

Abstract

Many cellular programs of neural development are under combinatorial regulation by different chemoattractive or chemorepulsive factors. Here, we describe a microfluidic platform that utilizes well-controlled three-dimensional (3D) diffusion to generate molecular gradients of varied steepness in a large array of hydrogel cylinders, allowing high-throughput 3D chemotactic assays for mechanistic dissection of steepness-dependent neuronal chemotaxis. Using this platform, we examine neuronal sensitivity to the steepness of gradient composed of netrin-1, nerve growth factor, or semaphorin3A (Sema3A) proteins, and reveal dramatic diversity and complexity in the associated chemotactic regulation of neuronal development. Particularly for Sema3A, we find that serine/threonine kinase-11 and glycogen synthase kinase-3 signaling pathways are differentially involved in steepness-dependent chemotactic regulation of coordinated neurite repellence and neuronal migration. These results provide insights to the critical role of gradient steepness in neuronal chemotaxis, and also prove the technique as an expandable platform for studying other chemoresponsive cellular systems.

Research Area(s)

  • COMMISSURAL AXON GUIDANCE, NERVE GROWTH CONES, SEMAPHORIN 3A, DEVELOPING NEOCORTEX, CORTICAL-NEURONS, SIGNALING MECHANISMS, HIPPOCAMPAL-NEURONS, NEURAL PROGENITORS, APICAL DENDRITES, RADIAL MIGRATION

Citation Format(s)

High-throughput three-dimensional chemotactic assays reveal steepness-dependent complexity in neuronal sensation to molecular gradients. / Xu, Zhen; Fang, Peilin; Xu, Bingzhe; Lu, Yufeng; Xiong, Jinghui; Gao, Feng; Wang, Xin; Fan, Jun; Shi, Peng.

In: Nature Communications, Vol. 9, 4745, 12.11.2018.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review

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