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DjFARP Contributes to the Regeneration and Maintenance of the Brain through Activation of DjRac1 in Dugesia japonica

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Abstract

FERM, RhoGEF, and Pleckstrin domain protein (FARP) mediated RhoGTPase pathways are involved in diverse biological processes, such as neuronal development and tumorigenesis. However, little is known about their role in neural regeneration. We uncovered for the first time that FARP-Rac1 signaling plays an important role in neural regeneration in Dugesia japonica, a planarian that possesses unparalleled regenerative capacities. The planarian FARP homolog DjFARP was primarily expressed in both intact and regenerating brain and pharynx tissue. Functional studies suggested that downregulation of DjFARP with dsRNA in Dugesia japonica led to smaller brain sizes, defects in brain lateral branches, and loss of cholinergic, GABAergic, and dopaminergic neurons in both intact and regenerating animals. Moreover, the Rho GTPase DjRac1 was shown to play a similar role in neural regeneration and maintenance. Rac1 activation assay showed that DjFARP acts as a guanine nucleotide exchange factor (GEF) for DjRac1. Together, these findings indicate that the brain defects seen in DjFARP knockdown animals may be attributable to DjRac1 inactivation. In conclusion, our study demonstrated that DjFARP-DjRac1 signaling was required for the maintenance and proper regeneration of the brain in Dugesia japonica.

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Data Availability

The datasets supporting the findings of this study are available from the corresponding author on reasonable request.

Abbreviations

AD:

Alzheimer’s disease

AP:

Anterior-posterior

BSA:

Bovine serum albumin

CNS:

Central nervous system

Co-IP:

Co- immunoprecipitation

dFISH:

Double fluorescent in situ hybridization

DH:

Dbl-homology

dpa:

Days post-amputation

FARP:

FERM, RhoGEF, and Pleckstrin domain protein

GEF:

Guanine nucleotide exchange factor

H3P:

Anti-phospho-histone H3

HRP:

Horseradish peroxidase

PCR:

Polymerase chain reaction

PD:

Parkinson’s disease

PH:

Pleckstrin homology

qPCR:

Real-time quantitative-PCR

RACE:

Rapid amplification of cDNA ends

RNAi:

RNA interference

TBST:

Tris-buffered saline with Tween20

WISH:

Whole-mount in situ hybridization

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Acknowledgements

We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (grant number 31970430, 32070459).

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Authors and Affiliations

  1. Laboratory of Developmental and Evolutionary Biology, Shandong University of Technology, 266 Xincun West Road, Zibo, 255049, People’s Republic of China

    Qian Song, Hui Zhen & Bosheng Zhao

  2. School of Life Sciences and Medicine, Shandong University of Technology, Zibo, 255049, China

    Huazhi Geng

  3. Zibo Maternal and Child Health Hospital, Zibo, 255000, China

    Hongjin Liu, Hongkuan Deng, Zuoqing Yuan, Jianyong Zhang, Zhonghong Cao, Qiuxiang Pang & Bosheng Zhao

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  1. Qian Song
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Contributions

Bosheng Zhao designed this work; Bosheng Zhao and Qian Song wrote the paper; Qian Song performed the experiments; Huazhi Geng, Hui Zhen, Hongjin Liu, Hongkuan Deng, Zuoqing Yuan, Jianyong Zhang, Zhonghong Cao, Qiuxiang Pang analyzed the data. All authors have approved the present version of the manuscript and have agreed to be accountable for all aspects of the work regarding questions related to the accuracy or integrity of any part of the work.

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Correspondence to Bosheng Zhao.

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All animal experiments complied with the ARRIVE guidelines and were carried out in accordance with the National Research Council’s Guide for the Care and Use of Laboratory Animals. The study protocol was approved by the Ethics Committee of Shandong University of Technology.

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Song, Q., Geng, H., Zhen, H. et al. DjFARP Contributes to the Regeneration and Maintenance of the Brain through Activation of DjRac1 in Dugesia japonica. Mol Neurobiol 60, 6294–6306 (2023). https://doi.org/10.1007/s12035-023-03478-6

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