Nystagmus‐related FRMD7 gene influences the maturation and complexities of neuronal processes in human neurons
Abstract Aims Idiopathic congenital nystagmus (ICN) is an oculomotor disorder caused by the defects in the ocular motor control regions of the brain. Mutations in FRMD7, a member of the FERM family of proteins, associated with cytoskeletal dynamics, are the most frequent causes of X‐linked ICN. Prev...
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doaj-6ab8d34c4da340eb9b27c2496ab325402020-11-25T03:54:55ZengWileyBrain and Behavior2162-32792019-12-01912n/an/a10.1002/brb3.1473Nystagmus‐related FRMD7 gene influences the maturation and complexities of neuronal processes in human neuronsJiali Pu0Shaobing Dai1Ting Gao2Jing Hu3Yi Fang4Ran Zheng5Chongyao Jin6Baorong Zhang7Department of Neurology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou ChinaDepartment of Anesthesiology Women's Hospital School Of Medicine Zhejiang University Hangzhou ChinaDepartment of Neurology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou ChinaDepartment of Neurology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou ChinaDepartment of Neurology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou ChinaDepartment of Neurology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou ChinaDepartment of Neurology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou ChinaDepartment of Neurology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou ChinaAbstract Aims Idiopathic congenital nystagmus (ICN) is an oculomotor disorder caused by the defects in the ocular motor control regions of the brain. Mutations in FRMD7, a member of the FERM family of proteins, associated with cytoskeletal dynamics, are the most frequent causes of X‐linked ICN. Previous studies illustrated that FRMD7 is involved in the elongation of neurites during neuronal development; however, almost all the studies were performed on mice cell models. The complexity in the human neuronal network might suggest a unique vulnerability of human neurons to FRMD7 mutations. Methods Herein, we successfully established human neuronal cell models with FRMD7 mutations, from fibroblasts‐reprogrammed neurons (iNs). In these neurons, the complexity of the neuronal processes was measured by the induced ratio, total neurite length, the number of terminals, and the number of maturation neurons. Results The complexity of the neuronal processes was greatly reduced during various reprogramming stages in the presence of FRMD7 mutations. Consistently, the expression of the three main Rho GTPases was significantly increased by FRMD7 mutations. Interestingly, a slightly diverse phenotype is observed in different derived neurons. Conclusion We established ideal human neuron models and confirmed that the mutation in FRMD7 influences the maturation and complexities of neuronal processes, which might be involved with the Rho GTPase signaling.https://doi.org/10.1002/brb3.1473CRISPR/Cas9FRMD7idiopathic congenital nystagmusinduced neuronsneuronal outgrowthRho GTPases |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jiali Pu Shaobing Dai Ting Gao Jing Hu Yi Fang Ran Zheng Chongyao Jin Baorong Zhang |
spellingShingle |
Jiali Pu Shaobing Dai Ting Gao Jing Hu Yi Fang Ran Zheng Chongyao Jin Baorong Zhang Nystagmus‐related FRMD7 gene influences the maturation and complexities of neuronal processes in human neurons Brain and Behavior CRISPR/Cas9 FRMD7 idiopathic congenital nystagmus induced neurons neuronal outgrowth Rho GTPases |
author_facet |
Jiali Pu Shaobing Dai Ting Gao Jing Hu Yi Fang Ran Zheng Chongyao Jin Baorong Zhang |
author_sort |
Jiali Pu |
title |
Nystagmus‐related FRMD7 gene influences the maturation and complexities of neuronal processes in human neurons |
title_short |
Nystagmus‐related FRMD7 gene influences the maturation and complexities of neuronal processes in human neurons |
title_full |
Nystagmus‐related FRMD7 gene influences the maturation and complexities of neuronal processes in human neurons |
title_fullStr |
Nystagmus‐related FRMD7 gene influences the maturation and complexities of neuronal processes in human neurons |
title_full_unstemmed |
Nystagmus‐related FRMD7 gene influences the maturation and complexities of neuronal processes in human neurons |
title_sort |
nystagmus‐related frmd7 gene influences the maturation and complexities of neuronal processes in human neurons |
publisher |
Wiley |
series |
Brain and Behavior |
issn |
2162-3279 |
publishDate |
2019-12-01 |
description |
Abstract Aims Idiopathic congenital nystagmus (ICN) is an oculomotor disorder caused by the defects in the ocular motor control regions of the brain. Mutations in FRMD7, a member of the FERM family of proteins, associated with cytoskeletal dynamics, are the most frequent causes of X‐linked ICN. Previous studies illustrated that FRMD7 is involved in the elongation of neurites during neuronal development; however, almost all the studies were performed on mice cell models. The complexity in the human neuronal network might suggest a unique vulnerability of human neurons to FRMD7 mutations. Methods Herein, we successfully established human neuronal cell models with FRMD7 mutations, from fibroblasts‐reprogrammed neurons (iNs). In these neurons, the complexity of the neuronal processes was measured by the induced ratio, total neurite length, the number of terminals, and the number of maturation neurons. Results The complexity of the neuronal processes was greatly reduced during various reprogramming stages in the presence of FRMD7 mutations. Consistently, the expression of the three main Rho GTPases was significantly increased by FRMD7 mutations. Interestingly, a slightly diverse phenotype is observed in different derived neurons. Conclusion We established ideal human neuron models and confirmed that the mutation in FRMD7 influences the maturation and complexities of neuronal processes, which might be involved with the Rho GTPase signaling. |
topic |
CRISPR/Cas9 FRMD7 idiopathic congenital nystagmus induced neurons neuronal outgrowth Rho GTPases |
url |
https://doi.org/10.1002/brb3.1473 |
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