Written by Jia Xiangbin

Editor in charge ︱ Wang Sizhen

Editor︱Yang Binwei

Neurodevelopmental Disorders (NDDs) are a wide range of neurological and psychiatric diseases caused by impaired brain development, including but not limited to autism spectrum disorder, intellectual disability, ADHD, communication impairment and learning disability, etc.

On August 17, 2022, Xia Kun's research group from Central South University/South China University, Shen Yiping's research group from Guangxi Zhuang Autonomous Region Maternal and Child Health Hospital/Boston Children's Hospital, and Guo Hui's research group from Central South University jointly published a paper entitled "De novo variants" on Science Advances.

Through international multi-center cooperation, the researchers collected a total of 12 patients with NDDs caused by UBAP2L gene mutation.

Figure 1.

(Image source: Jia X, Zhang S, et al.

To explore the role of the UBAP2L gene in neurodevelopment, the researchers constructed a Ubap2l gene knockout mouse model.

Figure 2.

(Image source: Jia X, Zhang S, et al.

In order to test the hypothesis of "whether stress granules (SGs) disorder is a possible common pathological mechanism of NDDs", the researchers further conducted enrichment analysis on SGs-related gene sets and NDDs-related gene sets, and found that NDDs-related gene sets, especially loneliness Symptom-related genes were significantly enriched in the core gene set of stress granule SGs
.

In order to identify more SG-related NDD genes, the researchers analyzed the de novo mutations of SGs-related genes carried by more than 40,000 NDDs individuals, and found a total of 29 de novo mutation rates of SGs genes that were not previously reported to be related to NDDs.
Significantly higher than the probability of random new mutations, including SG key core genes G3BP1 and G3BP2,
etc.

In response to these new mutations, the researchers confirmed that some of the new missense mutations in G3BP1 and G3BP2 significantly affected the formation of SGs using knockout cell lines and immunofluorescence staining
.

Notably, in CAPRIN1, another key gene regulating SG formation, a missense mutation in this gene was found to completely disrupt its binding to G3BP1/2, which is critical for SGs formation
.

Figure 3.
Co-expression of SG key core genes and PPI network

(Image source: Jia X, Zhang S, et al.
, Sci Adv, 2022)

Figure 4.
Research hypothesis: Variations in stress granule-related genes lead to disordered formation of SGs and thus participate in the occurrence of NDDs

(Source: Guo Hui Laboratory)

Conclusion and discussion, inspiration and prospect In summary, this study combines clinical genetics, cell biology, model organisms, bioinformatics and statistics to reveal the relationship between stress granules (SGs) SGs disorder and neural The potential causal relationship between developmental disorders (NDDs) suggests that SGs dysfunction may be one of the common pathological mechanisms of NDDs, and provides a possible entry point for the study of the mechanism of gene-environment interaction in the etiology of NDDs
.

The disadvantage is that this study does not have direct evidence that the disorder of SGs can lead to the occurrence of NDDs, only the correlation is discussed, and the follow-up still needs to use rescue experiments to determine the relationship between the two
.

Even though the etiology of more and more NDDs patients has been explained due to the development of sequencing technology, there are still many patients whose genetic evidence cannot reveal the etiology
.

Therefore, it is crucial to explore the influence of gene-environment interaction in the pathogenesis of NDDs
.

Original link: http://doi.
org/10.
1126/sciadv.
abo7112

Jia Xiangbin, a doctoral student from the Medical Genetics Research Center of Central South University, Dr.
Zhang Shujie from the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, and Tan Senwei, a doctoral student from the Central South University Medical Genetics Research Center are the co-first authors of the paper
.

This work has been strongly supported and helped by Associate Researcher Tan Jieqiong, Professor Yuan Ling, Professor Hu Zhengmao, and Professor Evan E.
Eichler from the University of Washington
.

Jia Xiangbin (2nd from left in 4th row), Du Bing (4th from left in 1st row), Guo Hui (3rd from left in 3rd row), Xia Kun (4th from left in 2nd row)

(Photo courtesy of: Xia Kun/Guo Hui Laboratory)

About the author (swipe up and down to read) 

Xia Kun's research group and Guo Hui's research group have long-term cooperation in the research direction of the genetic basis and pathogenesis of neurodevelopmental disorders, especially autism
.

The team has established research systems and platforms in human and medical genetics, genomics and bioinformatics, cell and molecular biology, and neurobiology
.

In recent years, he has published a series of research papers in academic journals such as J Clin Invest, Sci Adv (2 papers), Nat Commun, Mol Psychiatry (2 papers), AJHG, NAR, Circulation, Cell Rep, Brain and other academic journals
.

The team has been recruiting postdoctoral fellows for a long time.
For details, please refer to the recruitment announcement: Central South University Xia Kun's research group and Guo Hui's research group are jointly recruiting postdoctoral fellows.
Candidates should send their resumes and introductions to their main research results to guohui2@csu.
edu.
cn
.

Please indicate "Postdoctoral Application" in the subject of the email
.

Selected past articles

【1】Nat Commun︱Peng Yueqing's team discovered a new brain area that controls non-REM sleep

【2】eClinicalMedicine︱Wang Qing’s team reported Parkinson’s disease dementia related index determination: quantitative EEG, serum metabolism and inflammation

【3】Cell Biosci | Wang Yongjun's research group revealed the molecular mechanism of D-type dopachrome isomerase-mediated inflammatory response in injured spinal cord

【4】Neuron｜Hu Yang's group revealed a large number of genes that promote optic nerve regeneration and their significant neuroprotective effects in glaucoma mice

【5】Cereb Cortex︱Zhang Yuxuan's research group reveals the neurophysiological evidence of task modulation in speech processing

[6] Trends Cogn Sci︱Jiang Qiu team writes opinion articles on creative problem solving in knowledge-rich fields

【7】Front Aging Neurosci︱Hongmei Yu's team constructed a hierarchical multi-classification diagnosis framework for AD based on imaging features and clinical information

【8】J Neurosci︱Jin Mingyue/Guangchang Shinji's team revealed that α-Syn and tau play an important synergistic physiological function during brain development

【9】Cell Death Differ︱Xia Xiaobo's team revealed for the first time the relationship between "iron death" and the pathogenesis of glaucoma

【10】Sci Adv︱ Zeng Kewu/Tu Pengfei's team revealed a new target for the regulation of neuroinflammation by active ingredients of traditional Chinese medicine Yemazhui

Recommended high-quality scientific research training courses

[1] Symposium on Single-Cell Sequencing and Spatial Transcriptomics Data Analysis (August 27-28, Tencent Online Conference)

【2】Training course︱R language clinical prediction biomedical statistics special training

[3] Workshop on Metagenomics and Metabolomics R Language Analysis and Visualization (Tencent Conference on August 27)

Forum/Seminar Preview

【1】Forum Preview︱Brain·Machine Intelligence Fusion——Let the brain connect to the future, the brain science theme forum is the first time!

Welcome to "Logical Neuroscience" [1] Talent Recruitment︱"Logical Neuroscience" is looking for article interpretation/writing positions (part-time online, online office)

References (swipe up and down to read) 

[1]BP Coe, HAF Stessman, A.
Sulovari, MR Geisheker, TE Bakken, AM Lake, .
.
.
EE Eichler, Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity, Nat Genet, 2019, 51.

[2] P.
Anderson, N.
Kedersha, RNA granules: post-transcriptional and epigenetic modulators of gene expression, Nat Rev Mol Cell Biol, 2009, 10

End of this article