Transcriptional networks identify synaptotagmin-like 3 as a regulator of cortical neuronal migration during early neurodevelopment

Dong, Xinran; Yang, Lin; Liu, Kaiyi; Ji, Xiaoli; Tang, Chuanqing; Li, Wanxing; Ma, Ling; Mei, Yuting; Peng, Ting; Feng, Bo; Wu, Ziyan; Tang, Qi; Gao, Yongxing; Yan, Kai; Zhou, Wenhao; Xiong, Man

doi:10.1016/j.celrep.2021.108802

Cited by 5 publications

(3 citation statements)

References 58 publications

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“…Module 12 was increased in all γδ T cells and included genes involved in the γδ TCR signaling cascade ( *TRGC1 , BLK , and LAT2 ) ( Cibrian et al, 2020 ; Muro et al, 2019 ), GATA3 , a transcription factor expressed by most porcine γδ T cells ( Rodríguez-Gómez et al, 2019 ), and ID3 , an E protein inhibitor that controls the survival and expansion of γδ thymocytes ( Zhang et al, 2014 ). Module 13 segregated specifically with CD2 − γδ T cells and included SYTL3 , which regulates vesicular trafficking ( Dong et al, 2021 ); *CD163L1 (also known as WC1) and its variant *WC1.1 , which act as hybrid pattern recognition receptors and TCR coreceptors on bovine γδ T cells ( Herzig et al, 2010 ; Hsu et al, 2015 ); FHL2 , a transcriptional co-activator that regulates cell proliferation, survival, and motility ( Hua et al, 2016 ); and RHEX , which controls erythroid cell expansion ( Verma et al, 2014 ). The three remaining modules (14–16) exhibited subtle differences over pseudotime and did not segregate with specific cell clusters ( Figure 3C ).…”

Section: Resultsmentioning

confidence: 99%

A single-cell analysis of thymopoiesis and thymic iNKT cell development in pigs

Gu¹,

Madrid²,

Joyce³

et al. 2022

Cell Reports

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Section: Resultsmentioning

confidence: 99%

A single-cell analysis of thymopoiesis and thymic iNKT cell development in pigs

Gu¹,

Madrid²,

Joyce³

et al. 2022

Cell Reports

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“…Silencing of exophilin-6 has recently been shown to accelerate neuronal migration, which causes abnormal distribution of deep-layer neurons in brain organoids and reduces presynaptic neurotransmitter release in human embryonic stem cell-derived neurons (Dong et al, 2021).…”

Section: The Structure and Function Of Rab27 Effectorsmentioning

confidence: 99%

In vivo Roles of Rab27 and Its Effectors in Exocytosis

Izumi

2021

Cell Struct. Funct.

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The monomeric GTPase Rab27 regulates exocytosis of a broad range of vesicles in multicellular organisms. Several effectors bind GTP-bound Rab27a and/or Rab27b on secretory vesicles to execute a series of exocytic steps, such as vesicle maturation, movement along microtubules, anchoring within the peripheral F-actin network, and tethering to the plasma membrane, via interactions with specific proteins and membrane lipids in a local milieu. Although Rab27 effectors generally promote exocytosis, they can also temporarily restrict it when they are involved in the rate-limiting step. Genetic alterations in Rab27-related molecules cause discrete diseases manifesting pigment dilution and immunodeficiency, and can also affect common diseases such as diabetes and cancer in complex ways. Although the function and mechanism of action of these 2 effectors have been explored, it is unclear how multiple effectors act in coordination within a cell to regulate the secretory process as a whole. It seems that Rab27 and various effectors constitutively reside on individual vesicles to perform consecutive exocytic steps. The present review describes the unique properties and in vivo roles of the Rab27 system, and the functional relationship among different effectors coexpressed in single cells, with pancreatic beta cells used as an example.

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“…The second gene with the highest number of variants in our study, SYTL3, encodes a protein belonging to a family of peripheral membrane proteins that play a role in vesicular trafficking [76]. Recent studies show that SYTL3 regulates neuronal migration and neurotransmitter release in human neurons [77]. Whole-genome sequencing studies highlight SYTL3 as a new candidate gene for AD [78].…”

Section: Discussionmentioning

confidence: 78%

Identification of Neurotransmission and Synaptic Biological Processes Disrupted in Autism Spectrum Disorder Using Interaction Networks and Community Detection Analysis

Vilela,

Martiniano,

Marques

et al. 2023

Biomedicines

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Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by communication deficits and repetitive behavioral patterns. Hundreds of candidate genes have been implicated in ASD, including neurotransmission and synaptic (NS) genes; however, the genetic architecture of this disease is far from clear. In this study, we seek to clarify the biological processes affected by NS gene variants identified in individuals with ASD and the global networks that link those processes together. For a curated list of 1216 NS candidate genes, identified in multiple databases and the literature, we searched for ultra-rare (UR) loss-of-function (LoF) variants in the whole-exome sequencing dataset from the Autism Sequencing Consortium (N = 3938 cases). Filtering for population frequency was carried out using gnomAD (N = 60,146 controls). NS genes with UR LoF variants were used to construct a network of protein–protein interactions, and the network’s biological communities were identified by applying the Leiden algorithm. We further explored the expression enrichment of network genes in specific brain regions. We identified 356 variants in 208 genes, with a preponderance of UR LoF variants in the PDE11A and SYTL3 genes. Expression enrichment analysis highlighted several subcortical structures, particularly the basal ganglia. The interaction network defined seven network communities, clustering synaptic and neurotransmitter pathways with several ubiquitous processes that occur in multiple organs and systems. This approach also uncovered biological pathways that are not usually associated with ASD, such as brain cytochromes P450 and brain mitochondrial metabolism. Overall, the community analysis suggests that ASD involves the disruption of synaptic and neurotransmitter pathways but also ubiquitous, but less frequently implicated, biological processes.

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Transcriptional networks identify synaptotagmin-like 3 as a regulator of cortical neuronal migration during early neurodevelopment

Cited by 5 publications

References 58 publications

A single-cell analysis of thymopoiesis and thymic iNKT cell development in pigs

A single-cell analysis of thymopoiesis and thymic iNKT cell development in pigs

In vivo Roles of Rab27 and Its Effectors in Exocytosis

Identification of Neurotransmission and Synaptic Biological Processes Disrupted in Autism Spectrum Disorder Using Interaction Networks and Community Detection Analysis

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