Abnormal retinal development in the <i>Btrc</i> null mouse

Baguma-Nibasheka, Mark; Kablar, Boris

doi:10.1002/dvdy.22081

Cited by 15 publications

(4 citation statements)

References 46 publications

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“…340, of which 115 were intergenic variants, 197 were in introns of the BTRC gene, 27 were upstream variants of this gene and one was an upstream variant of the LBX1 gene. In mice, mutations in the BTRC gene are reported to affect spermatogenesis [ 32 ], mammary gland development [ 33 ], tumorigenesis [ 33 ] and retinal development [ 34 ]. Both BTRC [ 35 , 36 ] and LBX1 [ 36 ] have been associated with split-hand/split-foot malformations in humans.…”

Section: Discussionmentioning

confidence: 99%

Concordance analysis for QTL detection in dairy cattle: a case study of leg morphology

Berg

Fritz

Rodriguez

et al. 2014

Genetics Selection Evolution

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BackgroundThe present availability of sequence data gives new opportunities to narrow down from QTL (quantitative trait locus) regions to causative mutations. Our objective was to decrease the number of candidate causative mutations in a QTL region. For this, a concordance analysis was applied for a leg conformation trait in dairy cattle. Several QTL were detected for which the QTL status (homozygous or heterozygous for the QTL) was inferred for each individual. Subsequently, the inferred QTL status was used in a concordance analysis to reduce the number of candidate mutations.MethodsTwenty QTL for rear leg set side view were mapped using Bayes C. Marker effects estimated during QTL mapping were used to infer the QTL status for each individual. Subsequently, polymorphisms present in the QTL regions were extracted from the whole-genome sequences of 71 Holstein bulls. Only polymorphisms for which the status was concordant with the QTL status were kept as candidate causative mutations.ResultsQTL status could be inferred for 15 of the 20 QTL. The number of concordant polymorphisms differed between QTL and depended on the number of QTL statuses that could be inferred and the linkage disequilibrium in the QTL region. For some QTL, the concordance analysis was efficient and narrowed down to a limited number of candidate mutations located in one or two genes, while for other QTL a large number of genes contained concordant polymorphisms.ConclusionsFor regions for which the concordance analysis could be performed, we were able to reduce the number of candidate mutations. For part of the QTL, the concordant analyses narrowed QTL regions down to a limited number of genes, of which some are known for their role in limb or skeletal development in humans and mice. Mutations in these genes are good candidates for QTN (quantitative trait nucleotides) influencing rear leg set side view.

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Section: Discussionmentioning

confidence: 99%

Concordance analysis for QTL detection in dairy cattle: a case study of leg morphology

Berg

Fritz

Rodriguez

et al. 2014

Genetics Selection Evolution

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“…Our further study will focus on the scRNA-seq analysis of fovea region only, and explore its molecular features. [49][50][51]81 . Currently, the disease diagnosis and therapies were hampered by our understanding the development of human fetal retina.…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA-seq analysis maps the development of human fetal retina

Lü

et al. 2018

Preprint

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Vision starts with image formation at the retina, which contains diverse neuronal cell types that extract, process, and relay visual information to higher order processing centers in the brain. Though there has been steady progress in defining retinal cell types, very little is known about retinal development in humans, which starts well before birth. In this study, we performed transcriptomic profiling of developing human fetal retina from gestational weeks 12 to 27 using single-cell RNA-seq (scRNA-seq) and used pseudotime analysis to reconstruct the developmental trajectories of retinogenesis. Our analysis reveals transcriptional programs driving differentiation down four different cell types and suggests that Müller glia (MG) can serve as embryonic progenitors in early retinal development. In addition, we also show that transcriptional differences separate retinal progenitor cells (RPCs) into distinct subtypes and use this information to reconstruct RPC developmental trajectories and cell fate. Our results support a hierarchical program of differentiation governing cell-type diversity in the developing human retina. In summary, our work details comprehensive molecular classification of retinal cells, reconstructs their relationships, and paves the way for future mechanistic studies on the impact of gene regulation upon human retinogenesis.

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“…A β-TrCP1-deficient retina shows a complete absence of cholinergic amacrine cells (CACs), decrease in tyrosine hydroxylase-expressing amacrine cells, and reduction in the number of retinal ganglion cells. The population of precursors of CACs is reduced, whereas the population of precursors of retinal ganglion cells increases [96]. The intestine-specific tamoxifen-inducible ablation of both β-TrCP1 and β-TrCP2 results in β-catenin and IκBα stabilization and leads to mucositis, a deleterious gut mucosal inflammation resulting in mucosal barrier defects.…”

Section: Wnt Signaling Pathway and Its Regulation By Ubiquitin Ligmentioning

confidence: 99%

Ubiquitin Ligases Involved in the Regulation of Wnt, TGF-β, and Notch Signaling Pathways and Their Roles in Mouse Development and Homeostasis

Baloghová

Liďák

Cermak

2019

Genes

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The Wnt, TGF-β, and Notch signaling pathways are essential for the regulation of cellular polarity, differentiation, proliferation, and migration. Differential activation and mutual crosstalk of these pathways during animal development are crucial instructive forces in the initiation of the body axis and the development of organs and tissues. Due to the ability to initiate cell proliferation, these pathways are vulnerable to somatic mutations selectively producing cells, which ultimately slip through cellular and organismal checkpoints and develop into cancer. The architecture of the Wnt, TGF-β, and Notch signaling pathways is simple. The transmembrane receptor, activated by the extracellular stimulus, induces nuclear translocation of the transcription factor, which subsequently changes the expression of target genes. Nevertheless, these pathways are regulated by a myriad of factors involved in various feedback mechanisms or crosstalk. The most prominent group of regulators is the ubiquitin–proteasome system (UPS). To open the door to UPS-based therapeutic manipulations, a thorough understanding of these regulations at a molecular level and rigorous confirmation in vivo are required. In this quest, mouse models are exceptional and, thanks to the progress in genetic engineering, also an accessible tool. Here, we reviewed the current understanding of how the UPS regulates the Wnt, TGF-β, and Notch pathways and we summarized the knowledge gained from related mouse models.

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Abnormal retinal development in the Btrc null mouse

Cited by 15 publications

References 46 publications

Concordance analysis for QTL detection in dairy cattle: a case study of leg morphology

Concordance analysis for QTL detection in dairy cattle: a case study of leg morphology

Single-cell RNA-seq analysis maps the development of human fetal retina

Ubiquitin Ligases Involved in the Regulation of Wnt, TGF-β, and Notch Signaling Pathways and Their Roles in Mouse Development and Homeostasis

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