Krüppel‐like factor 7 deficiency disrupts corpus callosum development and neuronal migration in the developing mouse cerebral cortex DOI Creative Commons

Wentong Hong,

Pifang Gong,

Xinjie Pan

et al.

Brain Pathology, Journal Year: 2023, Volume and Issue: 33(5)

Published: July 3, 2023

Krüppel-like Factor 7 (KLF7) is a zinc finger transcription factor that has critical role in cellular differentiation, tumorigenesis, and regeneration. Mutations Klf7 are associated with autism spectrum disorder, which characterized by neurodevelopmental delay intellectual disability. Here we show KLF7 regulates neurogenesis neuronal migration during mouse cortical development. Conditional depletion of neural progenitor cells resulted agenesis the corpus callosum, defects neurogenesis, impaired neocortex. Transcriptomic profiling analysis indicated cohort genes involved differentiation migration, including p21 Rac3. These findings provide insights into our understanding potential mechanisms underlying neurological mutations.

Language: Английский

Cross-hemispheric communication: Insights on lateralized brain functions DOI
Sebastian Ocklenburg, Zengcai V. Guo

Neuron, Journal Year: 2024, Volume and Issue: 112(8), P. 1222 - 1234

Published: March 7, 2024

Language: Английский

Citations

21
ARID1B controls transcriptional programs of axon projection in an organoid model of the human corpus callosum DOI Creative Commons
Catarina Martins‐Costa,

Andrea Wiegers,

Vincent A. Pham

et al.

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(6), P. 866 - 885.e14

Published: May 7, 2024

Mutations in ARID1B, a member of the mSWI/SNF complex, cause severe neurodevelopmental phenotypes with elusive mechanisms humans. The most common structural abnormality brain ARID1B patients is agenesis corpus callosum (ACC), characterized by absence an interhemispheric white matter tract that connects distant cortical regions. Here, we find neurons expressing SATB2, determinant callosal projection neuron (CPN) identity, show impaired maturation ARID1B+/− neural organoids. Molecularly, reduction chromatin accessibility genomic regions targeted TCF-like, NFI-like, and ARID-like transcription factors drives differential expression genes required for (CC) development. Through vitro model CC tract, demonstrate this transcriptional dysregulation impairs formation long-range axonal projections, causing underconnectivity. Our study uncovers new functions during human corticogenesis, identifying cell-autonomous axonogenesis defects SATB2+ as ACC patients.

Language: Английский

Citations

14
Diverse axonal morphologies of individual callosal projection neurons reveal new insights into brain connectivity DOI Creative Commons
Suranjana Pal, Jonathan W. C. Lim, Linda J. Richards

et al.

Current Opinion in Neurobiology, Journal Year: 2024, Volume and Issue: 84, P. 102837 - 102837

Published: Jan. 24, 2024

Language: Английский

Citations

9
Functional connectivity and white matter microstructural alterations in patients with left basal ganglia acute ischemic stroke DOI

Meizhong Chen,

Yufan Wu, Yuntao Wang

et al.

Brain Imaging and Behavior, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Language: Английский

Citations

1
Symmetry in levels of axon-axon homophilic adhesion establishes topography in the corpus callosum and development of connectivity between brain hemispheres DOI
Alexandros Poulopoulos, Patrick Davis, Cheryl Brandenburg

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 31, 2024

Specific and highly diverse connectivity between functionally specialized regions of the nervous system is controlled at multiple scales, from anatomically organized following macroscopic axon tracts to individual target-finding synapse formation. Identifying mechanisms that enable entire subpopulations related neurons project their axons with regional specificity within stereotyped form appropriate long-range key understanding brain development, organization, function. Here, we investigate how cerebral cortex precise connections two cortical hemispheres via corpus callosum. We identify topographic principles developing trans-hemispheric callosal tract emerge through intrinsic guidance executed by growing in callosum first postnatal week mice. Using micro-transplantation regionally distinct neurons, subtype- specific growth cone purification, subcellular proteomics, utero gene manipulation, transhemispheric axons. find adhesion molecule levels instruct topography target field guidance. propose a model which transcallosal perform "handshake" guided co- fasciculation symmetric contralateral axons, resulting homotopic brain's hemispheres.

Language: Английский

Citations

7
NRF1 association with AUTS2-Polycomb mediates specific gene activation in the brain DOI Creative Commons
Sanxiong Liu, Kimberly A. Aldinger, Chi Vicky Cheng

et al.

Molecular Cell, Journal Year: 2021, Volume and Issue: 81(22), P. 4663 - 4676.e8

Published: Oct. 12, 2021

Language: Английский

Citations

39
FOXG1 sequentially orchestrates subtype specification of postmitotic cortical projection neurons DOI Creative Commons
Junhua Liu, Mengjie Yang,

Mingzhao Su

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(21)

Published: May 25, 2022

The mammalian neocortex is a highly organized six-layered structure with four major cortical neuron subtypes: corticothalamic projection neurons (CThPNs), subcerebral (SCPNs), deep callosal (CPNs), and superficial CPNs. Here, careful examination of multiple conditional knockout model mouse lines showed that the transcription factor FOXG1 functions as master regulator postmitotic specification found mice lacking functional exhibited deficits. Before embryonic day 14.5 (E14.5), enforces CPN identity in by activating Satb2 but repressing Bcl11b Tbr1. After E14.5, exerts distinct layers via differential regulation Tbr1, including versus CPNs enforcement CThPN identity. controls SCPN fate fine-tuning Fezf2 levels through diverse interactions SOX family proteins. Thus, our study supports developmental to explain subtypes sheds light on neuropathogenesis.

Language: Английский

Citations

28
Loss-of-function variants in MYCBP2 cause neurobehavioural phenotypes and corpus callosum defects DOI Creative Commons
Lama AlAbdi, Muriel Desbois, Domnița-Valeria Rusnac

et al.

Brain, Journal Year: 2022, Volume and Issue: 146(4), P. 1373 - 1387

Published: Oct. 6, 2022

Abstract The corpus callosum is a bundle of axon fibres that connects the two hemispheres brain. Neurodevelopmental disorders feature dysgenesis as core phenotype offer valuable window into pathology derived from abnormal development. Here, we describe cohort eight patients with neurodevelopmental disorder characterized by range deficits including abnormalities, developmental delay, intellectual disability, epilepsy and autistic features. Each patient harboured distinct de novo variant in MYCBP2, gene encoding an atypical really interesting new (RING) ubiquitin ligase signalling hub evolutionarily conserved functions We used CRISPR/Cas9 editing to introduce disease-associated variants residues Caenorhabditis elegans MYCBP2 orthologue, RPM-1, evaluated functional outcomes vivo. Consistent variable phenotypes variants, C. carrying corresponding human mutations rpm-1 displayed axonal behavioural abnormalities altered habituation. Furthermore, accumulation autophagy marker LGG-1/LC3 occurred affect RPM-1 activity. Functional genetic anatomical, cell biological readouts indicate are likely result loss function. Collectively, our results multiple CRISPR vivo animal model support direct link between spectrum term, MYCBP2-related delay defects (MDCD).

Language: Английский

Citations

25
Genetic heterogeneity in corpus callosum agenesis DOI Creative Commons
Monica-Cristina Pânzaru, Setalia Popa,

Ancuța Lupu

et al.

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 30, 2022

The corpus callosum is the largest white matter structure connecting two cerebral hemispheres. Agenesis of (ACC), complete or partial, one most common malformations in humans with a reported incidence ranging between 1.8 per 10,000 livebirths to 230-600 children and its presence associated neurodevelopmental disability. ACC may occur as an isolated anomaly component complex disorder, caused by genetic changes, teratogenic exposures vascular factors. Genetic causes are include partial chromosomal anomalies, autosomal dominant, recessive X-linked monogenic disorders, which can be either de novo inherited. extreme heterogeneity, illustrated large number syndromes ACC, highlight underlying complexity development. wide spectrum clinical manifestations from asymptomatic neonatal death. features epilepsy, motor impairment intellectual understanding heterogeneity essential for diagnosis, developing early intervention strategies, informed family planning. This review summarizes our current discusses latest discoveries.

Language: Английский

Citations

24
Based on white matter microstructure to early identify bipolar disorder from patients with depressive episode DOI
Hao Sun, Rui Yan,

Lingling Hua

et al.

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: 350, P. 428 - 434

Published: Jan. 21, 2024

Language: Английский

Citations

6