Impact of c-JUN deficiency on thalamus development in mice and human neural models DOI Creative Commons
Jiantao Shi, Qing Chen, Jiaming Lai

et al.

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 20, 2024

Abstract Background c-Jun is a key regulator of gene expression. Through the formation homo- or heterodimers, c-JUN binds to DNA and regulates transcription. While plays crucial role in embryonic development, its impact on nervous system development higher mammals, especially for some deep structures, example, thalamus diencephalon, remains unclear. Methods To investigate influence early knockout (KO) mice KO H1 stem cells (ESCs)-derived neural progenitor (NPCs), cerebral organoids (COs), (ThOs) models were used. We detected dysplasia via histological examination immunofluorescence staining, omics analysis, loss/gain function analysis. Results At day 14.5, exhibited sparseness fibers brain ventricular parenchyma malformation diencephalon. The absence accelerated induction NPCs but impaired extension human neuronal cultures. COs lacking displayed robust PAX6 + /NESTIN exterior layer lacked fibers-connected core. Moreover, subcortex-like areas defective characteristics with transcription factor 7 like 2-positive cells. Notably, guided ThOs, led inadequate patterning sparse internal nerve fibers. Chromatin accessibility analysis confirmed less accessible chromatin state genes related thalamus. Overexpression rescued these defects. RNA-seq identified 18 significantly down-regulated including RSPO2, WNT8B, MXRA5, HSPG2 PLAGL1 while 24 MSX1, CYP1B1, LMX1B, NQO1 COL2A1 up-regulated. Conclusion Our findings from vivo vitro experiments indicate that depletion impedes renders susceptible during mouse ThO patterning. work provides evidence first time play important roles thalamus/diencephalon development.

Language: Английский

Genetic determinants of skin ageing: a systematic review and meta-analysis of genome-wide association studies and candidate genes DOI Creative Commons

Chloe Wong,

Jun Yan Ng, Yang Yie Sio

et al.

Journal of PHYSIOLOGICAL ANTHROPOLOGY, Journal Year: 2025, Volume and Issue: 44(1)

Published: Feb. 8, 2025

Skin ageing is influenced by complex genetic factors. Various phenotypes such as wrinkling, pigmentation changes, and skin cancers have been linked to specific loci. However, the underlying mechanisms pathways remain poorly understood. This systematic review meta-analysis aims summarise loci found be associated with published genome-wide association studies (GWAS) candidate gene studies. We also evaluated overall of via identified patterns explore potential biological contributing ageing. The Web Science, Embase, PubMed databases were searched on January 2024 using exclusion criteria (e.g., study non-human subjects, focus diseases, or treatments) identify relevant articles. There did not appear any significant publication bias observed across all phenotypes. A total 48 included, revealing 30 that confirmed multiple AFG3L1P: odds ratio 1.133 95% confidence interval [1.044, 1.222]; BPIFA3: 1.859 [1.567, 2.151]; CLPTML1: 1.164 [1.0.99, 1.229]; CPNE7: 0.905 [0.852-0.958]; DEF8: 1.186 [1.042, 1.331]; IRF4: 1.260 [1.025, 1.495]; MYO16: 2.303 [1.697, 2.908]; PRDM16: 1.105 [1.084, 1.127]; RORA: 1.391 [1.206, 1.577]; SPG7: 0.922 [0.897, 0.947]; SPON1: 2.214 [1.204, 3.225]; SPTLC1: 1.464 [1.432, TYR: 1.175 [1.007, 1.343]). lack significance for many may due analysing different SNPs within same locus, weakening associations. Several phenotypic categories colour related, cancer wrinkling sagging related), suggesting shared are involved in pathogenesis pattern was several do a Despite heterogeneity among included use subjective visual methods phenotype assessment, our highlights critical role fundamental processes, development cellular organisation, Future research targets SNP populations could strengthen additional Further investigation into these processes would significantly advance understanding

Language: Английский

Citations

0
Axonal motor polyneuropathy in a 13 years old Girl with a de Novo variant in ADNP DOI

Sara Scaccini,

Carlo Alberto Cesaroni, Stefano Giuseppe Caraffi

et al.

Neurogenetics, Journal Year: 2025, Volume and Issue: 26(1)

Published: Feb. 24, 2025

Language: Английский

Citations

0
The Etiology of Moebius Syndrome—Making the Case for Animal Models DOI Open Access

Manuela-Petronela Tracicaru,

Rareș-Vasile Tracicaru, Delia Hînganu

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4217 - 4217

Published: April 29, 2025

Moebius syndrome (MBS) is a rare disease consisting of uni-/bilateral palsy CN VI and VII without impairment vertical eye movements. Its uncommon nature means that the etiology still uncertain. It thought to be caused by vascular lesions leading infarction in nuclei cranial nerves on posterior aspect pons. However, several genes have also been discussed as possibly causative. We performed literature search PUBMED database Science Direct platform with terms related pathology each individually. Included were original papers review articles published peer-reviewed international journals reference books databases subjects discussed. excluded not English, conference communications, dissertations, monographs, other non-peer-reviewed forms publication. The total number publications thus included was 62. This discusses functions three most found recent research (PLXND1, REV3L, TUBB3) results animal studies focusing their mutations. note PLXND1 REV3L mutations associated MBS current function suggest histological similar target disease, albeit clear phenotypic expression. ascertain TUBB3 are mostly CEFOM3, which differential diagnosis for MBS. Regarding etiology, we types involved discuss timing relation embryologic stages. highlight main investigation methods available. A multitude factors might causative MBS, consider it necessary attempt development an model disease. To this end, propose transgenic mice models containing single nucleotide documented human patients, use chick embryo etiology.

Language: Английский

Citations

0
Blood transcriptomic associations of epigenetic age in adolescents DOI Creative Commons
Dennis Khodasevich, Anne K. Bozack, Saher Daredia

et al.

Epigenetics, Journal Year: 2025, Volume and Issue: 20(1)

Published: May 16, 2025

Epigenetic aging in early life remains poorly characterized, and patterns of gene expression can provide biologically meaningful insights. Blood DNA methylation was measured using the Illumina EPICv1.0 array RNA sequencing performed blood 174 adolescent participants (age range: 14-15 years) from CHAMACOS cohort. Thirteen widely used epigenetic clocks were calculated, their associations with transcriptome-wide tested limma-voom pipeline. We found evidence for substantial shared between different clocks, including differential MYO6 ZBTB38 across five clocks. The epiTOC2, principal component (PC) PhenoAge, Hannum, PedBE PC Hannum associated highest number RNAs, exhibiting 22, 8, 5, 3, 2 transcripts respectively. Generally, biological more genes than chronological relative to CpG-trained counterparts. A total 17 our study replicated an independent adult sample 40-54 years). Our findings support relevance adolescents direction selection ageing biomarkers research.

Language: Английский

Citations

0
Biomarkers of mature neuronal differentiation and related diseases DOI Creative Commons
Xiaodong Yuan, Wen Li, Yan Qi

et al.

Future Science OA, Journal Year: 2024, Volume and Issue: 10(1)

Published: Oct. 21, 2024

The nervous system regulates perception, cognition and behavioral responses by serving as the body's primary communication for receiving, regulating transmitting information. Neurons are fundamental structures units of system. Their differentiation maturation processes rely on expression specific biomarkers. Neuron-specific intracellular markers can be used to determine degree neuronal maturation. Neuronal cytoskeletal proteins dictate shape structure neurons, while synaptic plasticity signaling intricately associated with markers. Furthermore, abnormal levels biomarkers serve diagnostic indicators diseases. This article reviews mature their relationship

Language: Английский

Citations

2
Abnormalities of Corpus Callosum and Other Interhemispheric Commissures DOI
Thierry A.G.M. Huisman, Thierry A.G.M. Huisman

Newborn, Journal Year: 2024, Volume and Issue: 3(2), P. 139 - 156

Published: June 21, 2024

Language: Английский

Citations

1
KIF21-associated peripheral neuropathy defined by impaired binding with TUBB3 DOI
Nicholas A. Borja, Mohammad Faraz Zafeer, Stephanie Bivona

et al.

Journal of Medical Genetics, Journal Year: 2024, Volume and Issue: unknown, P. jmg - 109908

Published: Dec. 6, 2024

KIF21A encodes a kinesin motor protein associated with isolated congenital fibrosis of the extraocular muscles (CFEOM), which occurs when autoinhibitory interaction between its and third coiled-coil domains is disrupted. In this study, we describe female child who heterozygous for novel de novo missense variant in p.Leu664Pro, located second domain that was absent her unaffected parents healthy population cohorts. She presented progressive peripheral neuropathy, hypoplasia corpus callosum strabismus absence CFEOM. Protein modelling predicts leads to significant alterations structure as well binding TUBB3. Co-immunoprecipitation data consistent decreased p.Leu664Pro TUBB3 vitro compared reference. Taken together, delineate -related phenotype defined by brain anomalies, developmental delay comitant potentially stemming from disruption

Language: Английский

Citations

1
Identification of two novel and one rare mutation in DYRK1A and prenatal diagnoses in three Chinese families with intellectual Disability-7 DOI Creative Commons
Cheng Huang,

Haiyan Luo,

Baitao Zeng

et al.

Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 14

Published: Dec. 20, 2023

Background and purpose: Intellectual disability-7 (MRD7) is a subtype disorder of intellectual disability (MRD) involving feeding difficulties, hypoactivity, febrile seizures at an age early onset, then progressive physical development deterioration. We purposed to identify the underlying causative genetic factors three individuals in each Chinese family who presented with symptoms facial dysmorphic features. provided prenatal diagnosis for families counseling prevention this disease. Methods: collected retrospective clinical diagnostic evidence probands our study, which included magnetic resonance imaging (MRI), computerized tomography (CT), electroencephalogram (EEG), intelligence tests study. Genetic investigation their next kin was performed by Trio-whole exome sequencing (WES). Sanger or quantitative PCR technologies were used as step verify variants confirmed Trio-WES families. Moreover, we amniocentesis explore state pathogenic fetuses molecular appropriate gestational period Results: The one fetus clinically diagnosed microcephaly exhibited developmental disability, postnatal Combining probands’ manifestations, uncovered heterozygous DYRK1A : novel variant exon3_exon4del p.(Gly4_Asn109del), c.1159C>T p.(Gln387*), previously but rare c.1309C>T p.(Arg437*) (NM_001396.5) families, respectively. In light updated American College Medical Genomics (ACMG) criterion, both classified likely (PSV1+PM6), while c1309C>T identified (PVS1+PS2_Moderate+PM2). Considering features testimony, MRD7. These discovered considered causal mutations Prenatal detected dominant p.(Gln387*) fetuses, indicating significant probability MRD7, subsequently gestation intervened parents’ determination professional obstetrical operation. On other side, testing revealed wild-type alleles two parents decided sustain gestation. Conclusion: mutation has broadened spectrum MRD7 level. Besides, study supported determine efficiently provide concise using technology.

Language: Английский

Citations

3
Profiling of immune infiltration landscape of ruptured intracranial aneurysm DOI Creative Commons
Chenglong Li, Zhe Su,

Wenjing Su

et al.

Medicine, Journal Year: 2024, Volume and Issue: 103(12), P. e37523 - e37523

Published: March 22, 2024

Previous research has indicated that the rupture of intracranial aneurysm (IA) is a significant contributor to mortality from stroke. The objective this present study was examine infiltration patterns in ruptured (RIA), with aim generating insights could inform development effective immunotherapeutic approaches.

Language: Английский

Citations

0
Clinical and genetic characteristics of Chinese patients with congenital fibrosis of the extraocular muscles DOI Creative Commons
Jin Wu, Lijuan Huang,

Yunyu Zhou

et al.

Orphanet Journal of Rare Diseases, Journal Year: 2024, Volume and Issue: 19(1)

Published: Aug. 15, 2024

Abstract Objective This study aimed to describe the clinical and genetic characteristics of Chinese patients with congenital fibrosis extraocular muscles (CFEOM), evaluate phenotype–genotype correlations in these patients. Methods was a retrospective study. Patients CFEOM underwent detailed ophthalmic examinations magnetic resonance imaging (MRI). Panel-based next-generation sequencing performed identify pathogenic variants disease-causing genes. Results Sixty-two were recruited into this Thirty-nine diagnosed CFEOM1 23 CFEOM3. Forty-nine 62 carried either KIF21A (41/49) or TUBB3 (8/49). Six known missense genes, novel variant (c.3906T > A, p.D1302E) gene detected. Most carrying mutation displayed isolated CFEOM, whereas CFEOM3 had wide range manifestations, alone syndromes. Nystagmus also present 12 CFEOM. Furthermore, MRI findings varied, ranging from attenuation dysgenesis cranial nerves brain structure. Conclusions The identified will further expand spectrum CFEOM-related However, no established because diversity

Language: Английский

Citations

0