5.9
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5.9
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2023 Vol. 50, No. 2

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Review
Planar cell polarity regulators in asymmetric organogenesis during development and disease
De-Li Shi
2023, 50(2): 63-76. doi: 10.1016/j.jgg.2022.06.007
Abstract (248) PDF (25)
Abstract:
The phenomenon of planar cell polarity is critically required for a myriad of morphogenetic processes in metazoan and is accurately controlled by several conserved modules. Six “core” proteins, including Frizzled, Flamingo (Celsr), Van Gogh (Vangl), Dishevelled, Prickle, and Diego (Ankrd6), are major components of the Wnt/planar cell polarity pathway. The Fat/Dchs protocadherins and the Scrib polarity complex also function to instruct cellular polarization. In vertebrates, all these pathways are essential for tissue and organ morphogenesis, such as neural tube closure, left–right symmetry breaking, heart and gut morphogenesis, lung and kidney branching, stereociliary bundle orientation, and proximal–distal limb elongation. Mutations in planar polarity genes are closely linked to various congenital diseases. Striking advances have been made in deciphering their contribution to the establishment of spatially oriented pattern in developing organs and the maintenance of tissue homeostasis. The challenge remains to clarify the complex interplay of different polarity pathways in organogenesis and the link of cell polarity to cell fate specification. Interdisciplinary approaches are also important to understand the roles of mechanical forces in coupling cellular polarization and differentiation. This review outlines current advances on planar polarity regulators in asymmetric organ formation, with the aim to identify questions that deserve further investigation.
Original research
ftr82 is necessary for hair cell morphogenesis and auditory function during zebrafish development
Guoli Yin, Fuping Qian, Jia Yao, Ziyang Wang, Xin Wang, Dong Liu, Cheng Wang
2023, 50(2): 77-86. doi: 10.1016/j.jgg.2022.11.008
Abstract (282) PDF (40)
Abstract:
Damages of sensory hair cells (HCs) are mainly responsible for sensorineural hearing loss, while the pathological mechanism remains not fully understood due to the many potential deafness genes unidentified. ftr82, a member of the largely TRIMs family in fish, has been found specifically expressed in the otic vesicle while its function is still unclear. Here, we investigate the roles of ftr82 in HC development and hearing function utilizing the zebrafish model. The results of in situ hybridization illustrate that ftr82 is always restricted to localize in otic vesicles at different stages. The defects of HCs are observed both in ftr82 morphants and mutants, including significantly decreased crista HCs, shortened cilia as well as remarkably reduced functional HCs in neuromasts, which could be successfully rescued by co-injection of exogenous ftr82 mRNA. The behavior assay of startle response indicates that larvae lacking of ftr82 exhibits lower sensitivity to external sound stimuli. Further research reveals that the loss of HCs is mainly caused by cell apoptosis mediated by caspase-3 activation. Our study demonstrates that ftr82 is a crucial hearing-related gene that regulates the HC morphogenesis and auditory function performing, which provides new insight into the rapid identification of the deafness gene.
PRMT5 determines the pattern of polyploidization and prevents liver from cirrhosis and carcinogenesis
Jincheng Wang, Xiang Huang, Daoshan Zheng, Qiuling Li, Mei Mei, Shilai Bao
2023, 50(2): 87-98. doi: 10.1016/j.jgg.2022.04.008
Abstract (302) PDF (25)
Abstract:
Human hepatocellular carcinoma (HCC) occurs almost exclusively in cirrhotic livers. Here, we report that hepatic loss of protein arginine methyltransferase 5 (PRMT5) in mice is sufficient to cause cirrhosis and HCC in a clinically relevant way. Furthermore, pathological polyploidization induced by hepatic loss of PRMT5 promotes liver cirrhosis and hepatic tumorigenesis in aged liver. The loss of PRMT5 leads to hyper-accumulation of P21 and endoreplication-dependent formation of pathological mono-nuclear polyploid hepatocytes. PRMT5 and symmetric dimethylation at histone H4 arginine 3 (H4R3me2s) directly associate with chromatin of P21 to suppress its transcription. More importantly, loss of P21 rescues the pathological mono-nuclear polyploidy and prevents PRMT5-deficiency-induced liver cirrhosis and HCC. Thus, our results indicate that PRMT5-mediated symmetric dimethylation at histone H4 arginine 3 (H4R3me2s) is crucial for preventing pathological polyploidization, liver cirrhosis and tumorigenesis in mouse liver.
Infection of SARS-CoV-2 causes severe pathological changes in mouse testis
Min Chen, Shihua Li, Shujun Liu, Yuhang Zhang, Xiuhong Cui, Limin Lv, Bowen Liu, Aihua Zheng, Qihui Wang, Shuguang Duo, Fei Gao
2023, 50(2): 99-107. doi: 10.1016/j.jgg.2022.11.011
Abstract (224) PDF (9)
Abstract:
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected more than 600 million people worldwide. Several organs including lung, intestine, and brain are infected by SARS-CoV-2. It has been reported that SARS-CoV-2 receptor angiotensin-converting enzyme-2 (ACE2) is expressed in human testis. However, whether testis is also affected by SARS-CoV-2 is still unclear. In this study, we generate a human ACE2 (hACE2) transgenic mouse model in which the expression of hACE2 gene is regulated by hACE2 promoter. Sertoli and Leydig cells from hACE2 transgenic mice can be infected by SARS-CoV-2 pseudovirus in vitro, and severe pathological changes are observed after injecting the SARS-CoV-2 pseudovirus into the seminiferous tubules. Further studies reveal that Sertoli and Leydig cells from hACE2 transgenic mice are also infected by authentic SARS-CoV-2 virus in vitro. After testis interstitium injection, authentic SARS-CoV-2 viruses are first disseminated to the interstitial cells, and then detected inside the seminiferous tubules which in turn cause germ cell loss and disruption of seminiferous tubules. Our study demonstrates that testis is most likely a target of SARS-CoV-2 virus. Attention should be paid to the reproductive function in SARS-CoV-2 patients.
primiReference: a reference for analysis of primary-microRNA expression in single-nucleus sequencing data
Amy E. Elias, Thomas A. Nuñez, Bianca Kun, Jill A. Kreiling
2023, 50(2): 108-121. doi: 10.1016/j.jgg.2022.10.003
Abstract (358) PDF (17)
Abstract:
Single-nucleus RNA-sequencing technology has revolutionized understanding of nuanced changes in gene expression between cell types within tissues. Unfortunately, our understanding of regulatory RNAs, such as microRNAs (miRNAs), is limited through both single-cell and single-nucleus techniques due to the short length of miRNAs in the cytoplasm and the incomplete reference of longer primary miRNA (pri-miRNA) transcripts in the nucleus. We build a custom reference to align and count pri-miRNA sequences in single-nucleus data. Using young and aged subventricular zone (SVZ) nuclei, we show differential expression of pri-miRNAs targeting genes involved in neural stem cells (NSC) differentiation in the aged SVZ. Furthermore, using wild-type and 5XFAD mouse model cortex nuclei, to validate the use of primiReference, we find cell-type-specific expression of pri-miRNAs known to be involved in Alzheimer's disease (AD). pri-miRNAs likely contribute to NSC dysregulation with age and AD pathology. primiReference is paramount in capturing a global profile of gene expression and regulation in single-nucleus data and can provide key insights into cell-type-specific expression of pri-miRNAs, paving the way for future studies of regulation and pathway dysregulation. By looking at pri-miRNA abundance and transcriptional differences, regulation of gene expression by miRNAs in disease and aging can be further explored.
Letter to the editor
Absence of Serpinb6a causes progressive hair cell apoptosis and hearing loss in mice
Cheng Cheng, Jieyu Qi, Liyan Zhang, He Li, Jie Lu, Siyu Li, Zhong Zhang, Yue Qiu, Chen Zhang, Lulu Jiang, Chaorong Yu, Xia Gao, Phillip I. Bird, Renjie Chai
2023, 50(2): 122-125. doi: 10.1016/j.jgg.2022.08.006
Abstract (409) PDF (35)
Abstract:
Microtubules are essential for angiogenic sprout elongation in zebrafish
Chuan Wu, Da Zhang, Jingying Chen
2023, 50(2): 126-129. doi: 10.1016/j.jgg.2022.08.005
Abstract (522) PDF (46)
Abstract:
A heavy metal transporter gene ZmHMA3a promises safe agricultural production on cadmium-polluted arable land
Yuanyuan Chen, Zhen-Fei Chao, Min Jin, Ya-Ling Wang, Yaoyao Li, Jia-Chen Wu, Yingjie Xiao, Yong Peng, Qiao-Yan Lv, Songtao Gui, Xiaqing Wang, Mei-Ling Han, Alisdair R. Fernie, Dai-Yin Chao, Jianbing Yan
2023, 50(2): 130-134. doi: 10.1016/j.jgg.2022.08.003
Abstract (491) PDF (67)
Abstract:
FISH-based “pan” and “core” karyotypes reveal genetic diversification of Roegneria ciliaris
Menghao Cheng, Xingyue Li, Huimin Cui, Haojie Sun, Tianshuo Deng, Xinying Song, Rongrong Song, Tong Wang, Zongkuan Wang, Haiyan Wang, Xiue Wang
2023, 50(2): 135-138. doi: 10.1016/j.jgg.2022.06.005
Abstract (494) PDF (36)
Abstract:
Corrigendum to “AMPK controls sucrose taste sensitization in Drosophila” [Journal of Genetics and Genomics (2023) 50, 50–53]
Yun Hu, Zhi-Ying Liu, Sha-Sha Li, An-Qi Li, G Gregory Neely, Qiao-Ping Wang
2023, 50(2): 139-139. doi: 10.1016/j.jgg.2023.01.005
Abstract (113) PDF (5)
Abstract: