NEDL2 is an essential regulator of enteric neural development and GDNF/Ret signaling

Wei, Ru‐Dong; Qiu, Xiao‐Bo; Wang, Shaoxia; Li, Yang; Wang, Yiwu; Lu, Kefeng; Fu, Yesheng; Xing, Guichun; He, Fuchu; Zhang, Lingqiang

doi:10.1016/j.cellsig.2014.12.013

Cited by 18 publications

(26 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Differing in allele frequency across three population comparisons and associated with the abundance of Clostridiales, the genetic variant rs7587067 has a significantly higher frequency in African (minor allele frequency [MAF] = 0.802) versus East Asian (MAF = 0.190, F ST = 0.54, Chromosome = 98.7%, Genome-Wide = 98.9%), admixed American (MAF = 0.278, F ST = 0.44, Chromosome = 99.0%, Genome-Wide = 99.1%), and European populations (MAF = 0.267, F ST = 0.45, Chromosome = 98.7.3%, Genome-Wide = 98.7%). This intronic variant for the gene HECW2 is a known expression quantitative trait locus (eQTL) (GTEx, eQTL Effect Size = -0.18, p = 7.4e-5) [72,73], and HECW2 encodes a ubiquitin ligase linked to enteric gastrointestinal nervous system function through maintenance of endothelial lining of blood vessels [74,75]. Knockout of HECW2 in mice reduced enteric neuron networks and gut motility, and patients with Hirschsprungs disease have diminished localization of HECW2 to regions affected by loss of neurons and colon blockage when compared to other regions of their own colon and healthy individuals [76].…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota diversity across ethnicities in the United States

et al. 2018

View full text Add to dashboard Cite

Composed of hundreds of microbial species, the composition of the human gut microbiota can vary with chronic diseases underlying health disparities that disproportionally affect ethnic minorities. However, the influence of ethnicity on the gut microbiota remains largely unexplored and lacks reproducible generalizations across studies. By distilling associations between ethnicity and differences in two US-based 16S gut microbiota data sets including 1,673 individuals, we report 12 microbial genera and families that reproducibly vary by ethnicity. Interestingly, a majority of these microbial taxa, including the most heritable bacterial family, Christensenellaceae, overlap with genetically associated taxa and form co-occurring clusters linked by similar fermentative and methanogenic metabolic processes. These results demonstrate recurrent associations between specific taxa in the gut microbiota and ethnicity, providing hypotheses for examining specific members of the gut microbiota as mediators of health disparities.

show abstract

Section: Discussionmentioning

confidence: 99%

Gut microbiota diversity across ethnicities in the United States

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Differing in allele frequency across three population comparisons and associated with the abundance of Clostridiales, the genetic variant rs7587067 has a significantly higher frequency in African (Minor Allele Frequency (MAF)=0.802) versus East Asian (MAF=0.190, F ST =0.54, Chromosome=98.7%, Genome-Wide=98.9%), admixed American (MAF=0.278, F ST =0.44, Chromosome=99.0%, Genome-Wide=99.1%), and European populations (MAF=0.267, F ST =0.45, Chromosome=98.7.3%, Genome-Wide=98.7%). This intronic variant for the gene HECW2 is a known eQTL (GTeX, eQTL Effect Size=−0.18, p=7.4e-5) (71, 72), and HECW2 encodes a ubiquitin ligase linked to enteric gastrointestinal nervous system function through maintenance of endothelial lining of blood vessels (73, 74). Knockout of HECW2 in mice reduced enteric neuron networks and gut motility, and patients with Hirschsprung’s disease have diminished localization of HECW2 to regions affected by loss of neurons and colon blockage when compared to other regions of their own colon and healthy individuals (75).…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota Diversity across Ethnicities in the United States

Brooks

Priya

Blekhman

et al. 2018

Preprint

View full text Add to dashboard Cite

32Composed of hundreds of microbial species, the composition of the human gut 33 microbiota can vary with chronic diseases underlying health disparities that 34 disproportionally affect ethnic minorities. However, the influence of ethnicity on the gut 35 microbiota remains largely unexplored and lacks reproducible generalizations across 36 studies. By distilling associations between ethnicity and differences in two United States 37 based 16S gut microbiota datasets including 1,673 individuals, we report 12 microbial 38 genera and families that reproducibly vary by ethnicity. Interestingly, a majority of these 39 microbial taxa, including the most heritable bacterial family, Christensenellaceae, overlap 40 with genetically-associated taxa and form co-occurring clusters linked by similar 41 fermentative and methanogenic metabolic processes. These results demonstrate recurrent 42 associations between specific taxa in the gut microbiota and ethnicity, providing hypotheses 43 for examining specific members of the gut microbiota as mediators of health disparities. 44Here, we comprehensively examine connections between self-declared ethnicity and 68 gut microbiota differences across more than a thousand individuals sampled by the 69 American Gut Project (AGP, N=1375) (24) and the Human Microbiome Project (HMP, N=298) 70 (6). Previous studies demonstrated that human genetic diversity in the HMP associates with 71 differences in microbiota composition (25), and genetic population structure within the HMP 72 generally delineates self-declared ethnicity (20). Ethnicity was not found to have a 73 significant association with microbiota composition in a Middle Eastern population, 74 however factors such as lifestyle and environment that influence microbiota variation across 75 participants was homogenous compared to the ethnic, sociocultural, economic, and dietary 76 diversity found within the United States (26). While ethnic diversity is generally 77 underrepresented in current microbiota studies, evidence supporting an ethnic influence on 78 microbiota composition among first generation immigrants has been recently demonstrated 79 in a Dutch population (27). The goal of this examination is to evaluate, for the first time, if 80 there are reproducible differences in gut microbiota across ethnicities within an overlapping 81 United States population, as ethnicity is one of the key defining factors for health disparity 82 incidence in the United States. Lifestyle, dietary, and genetic factors all vary to different 83 degrees across ethnic groups in the United States, and it will require more even sampling of 84 ethnic diversity and stricter phenotyping of study populations to disentangle which factors 85 underlie ethnic microbiota variation in the AGP and HMP. 86 6 Results: 87 Microbiota are subtly demarcated by ethnicity 88We first evaluate gut microbiota distinguishability between AGP ethnicities (Fig 1A, 89 family taxonomic level, Asians-Pacific Islanders (N=88), Caucasians (N=1237), Hispanics 90 (N=37), and African Americ...

show abstract

“…Previous studies indicate that human HECW1 and HECW2 are preferentially expressed in neuronal tissue 10,11 . Analysis of various Drosophila organs by qPCR and immunoblotting, revealed a preferential expression of Hecw in the fly gonads and central nervous system (Fig.…”

Section: Cg42797/hecw Is the Drosophila Ortholog Of Hecw1 And Hecw2mentioning

confidence: 98%

The ubiquitin ligase Hecw controls oogenesis and neuronal homeostasis by promoting the liquid state of ribonucleoprotein particles

Fajner

Giavazzi

Sala

et al. 2020

Preprint

View full text Add to dashboard Cite

Specialised ribonucleoprotein (RNP) granules are a hallmark of germ cells. Among their main function is the spatial and temporal modulation of the activity of specific mRNA transcripts that allow specification of primary embryonic axes. While RNPs composition and role are well established, their regulation is poorly defined. Here, we demonstrate that Hecw, a newly identified Drosophila ubiquitin ligase, is a key modulator of RNPs in oogenesis. Loss of Hecw activity results in the formation of enlarged granules that transition from a liquid to a gel-like state. At the molecular level, Hecw depletion leads to reduced ubiquitination and activity of the translational repressor Fmrp, resulting in premature Orb expression/recruitment in nurse cells. In addition to defective oogenesis, flies lacking Hecw show neurodegenerative traits with premature aging and climbing defects due to neuronal loss that are linked to RNPs condensation. Our findings reveal an unprecedented function of ubiquitin in modulating RNP fluidity and activity.

show abstract

NEDL2 is an essential regulator of enteric neural development and GDNF/Ret signaling

Cited by 18 publications

References 30 publications

Gut microbiota diversity across ethnicities in the United States

Gut microbiota diversity across ethnicities in the United States

Gut Microbiota Diversity across Ethnicities in the United States

The ubiquitin ligase Hecw controls oogenesis and neuronal homeostasis by promoting the liquid state of ribonucleoprotein particles

Contact Info

Product

Resources

About