Local cortical inhibitory subnetworks are shaped by pyramidal neuron progenitor type DOI Open Access
Gemma Gothard, Kashif Mahfooz, Sarah E. Newey

et al.

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

Published: Oct. 7, 2024

Abstract The degree to which cortical neurons share inhibitory synaptic input determines their co-activity within a network. However, the principles by inhibition is shared between are not known. Here we combine in utero labeling with vivo two-photon targeted patch-clamp recordings mature cortex reveal that layer 2/3 (L2/3) pyramidal neuron’s local reflects embryonic progenitor type from neuron born. In contrast neighboring neurons, derived intermediate progenitors receive weakly coupled network activity. underlying mechanisms do depend upon amount of received different interneuron subclasses. Rather, defines how much shares its neighbors, reflected individual interneurons target according type. These findings new significance for diversity and identify ontogenetic origins fine-scale subnetworks.

Language: Английский

Making Ramón y Cajal proud: Development of cell identity and diversity in the cerebral cortex DOI
Daniela J. Di Bella, Nuria Domıńguez-Iturza, Juliana Brown

et al.

Neuron, Journal Year: 2024, Volume and Issue: 112(13), P. 2091 - 2111

Published: May 15, 2024

Language: Английский

Citations

16
Human neural stem cells derived from fetal human brain communicate with each other and rescue ischemic neuronal cells through tunneling nanotubes DOI Creative Commons

D. L. Capobianco,

Roberta De Zio, Daniela Celeste Profico

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(8)

Published: Sept. 1, 2024

Abstract Pre-clinical trials have demonstrated the neuroprotective effects of transplanted human neural stem cells (hNSCs) during post-ischemic phase. However, exact mechanism remains unclear. Tunneling nanotubes (TNTs) are long plasma membrane bridges that physically connect distant cells, enabling intercellular transfer mitochondria and contributing to repair processes. Whether hNSCs communicate through TNTs their role in neuroprotection unknown. In this study, non-immortalized hNSC lines derived from fetal brain tissues were examined explore these possibilities assess potential hNSCs. Using Tau-STED super-resolution confocal microscopy, live cell time-lapse fluorescence electron direct or non-contact homotypic co-cultures, we generate nestin-positive both 3D neurospheres 2D cultures, which they functional mitochondria. Co-culturing with differentiated SH-SY5Y ( d SH-SY5Y) revealed heterotypic allowing mitochondrial SH-SY5Y. To investigate neuroprotection, subjected oxygen-glucose deprivation (OGD) followed by reoxygenation (OGD/R) without co-cultures. Compared normoxia, OGD/R became apoptotic impaired electrical activity. When co-cultured contact hNSCs, enabled SH-SY5Y, rescuing them apoptosis restoring bioelectrical profile toward normoxic This complete did not occur co-culture. summary, our data reveal presence a network containing nestin within demonstrate involvement mediated highlight strong efficacy neuroprotection.

Language: Английский

Citations

6
Multipotent progenitors instruct ontogeny of the superior colliculus DOI Creative Commons
Giselle Cheung, Florian M. Pauler, Peter Koppensteiner

et al.

Neuron, Journal Year: 2023, Volume and Issue: 112(2), P. 230 - 246.e11

Published: Dec. 13, 2023

The superior colliculus (SC) in the mammalian midbrain is essential for multisensory integration and composed of a rich diversity excitatory inhibitory neurons glia. However, developmental principles directing generation SC cell-type are not understood. Here, we pursued systematic cell lineage tracing silico vivo, preserving full spatial information, using genetic mosaic analysis with double markers (MADM)-based clonal single-cell sequencing (MADM-CloneSeq). clonally related lineages revealed that radial glial progenitors (RGPs) exceptionally multipotent. Individual resident RGPs have capacity to produce all neuron types, even at stage terminal division. While individual units show no pre-defined cellular composition, establishment appropriate relative proportions distinct neuronal types occurs PTEN-dependent manner. Collectively, our findings provide an inaugural framework single-RGP/-cell level ontogeny.

Language: Английский

Citations

11
Continuous cell type diversification throughout the embryonic and postnatal mouse visual cortex development DOI Creative Commons
Yuan Gao, Cindy T. J. van Velthoven, Changkyu Lee

et al.

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

Published: Oct. 6, 2024

The mammalian cortex is composed of a highly diverse set cell types and develops through series temporally regulated events that build out the type circuit foundation for cortical function. mechanisms underlying development different remain elusive. Single-cell transcriptomics provides capacity to systematically study across entire temporal range development. Here, we present comprehensive high-resolution transcriptomic epigenomic atlas developing mouse visual cortex. was built from single-cell RNA-sequencing dataset 568,674 high-quality transcriptomes single-nucleus Multiome 194,545 nuclei providing both chromatin accessibility profiles, densely sampled throughout embryonic postnatal developmental stages E11.5 P56. We computationally reconstructed trajectory map all excitatory, inhibitory, non-neuronal in cortex, identifying branching points marking emergence new at specific ages defining molecular signatures cellular diversification. In addition neurogenesis, gliogenesis early postmitotic maturation stage which gives rise classes nearly subclasses, find increasingly refined emerge differentiation process, including late many during eye-opening (P11-P14) onset critical period (P21), suggesting continuous diversification Throughout development, cooperative dynamic changes gene expression types, peaks potentially regulating genes transcription factors peaks. Furthermore, single can be by multiple associated with and/or stages. Collectively, our most detailed directly individual reveals logic refinement identities

Language: Английский

Citations

4
Probing Cell-Type Specificity of Mutant Phenotype at Transcriptomic Level Using Mosaic Analysis with Double Markers (MADM) DOI
Giselle Cheung, Florian M. Pauler, Simon Hippenmeyer

et al.

Methods in molecular biology, Journal Year: 2025, Volume and Issue: unknown, P. 139 - 151

Published: Jan. 1, 2025

Language: Английский

Citations

0
Clonal lineage tracing and transcriptomics of cortical progenitor populations reveal maintenance of differentiation potential DOI Creative Commons
Danyon Harkins,

Shawar Ali,

Teodora Tockovska

et al.

Stem Cell Reports, Journal Year: 2025, Volume and Issue: unknown, P. 102418 - 102418

Published: Feb. 1, 2025

Postnatal neocortical development is a complex period wherein radial glial progenitors (RGPs) complete excitatory neurogenesis and transition to the production of glia. Here, we take advantage multi-layered lineage tracing tool pbacBarcode, examine contributions individual cortical RGPs postnatal cortex. We reveal that some are multipotent give rise olfactory bulb interneurons, astrocytes, oligodendrocytes in ∼2:1:1 ratio. provide evidence differentiation potential into terminal cell types maintained as late post-natal day (P)4, suggesting population decline model, opposed fate restriction, underlies development. Moreover, pool proliferative intermediary cells, which may represent intermediate progenitor population, contribute three major types. Lastly, RGP contribution show oligodendrocyte founder by largely P3.

Language: Английский

Citations

0
How radial glia progenitor lineages generate cell-type diversity in the developing cerebral cortex DOI Creative Commons
Fabrizia Pipicelli, Ana Villalba, Simon Hippenmeyer

et al.

Current Opinion in Neurobiology, Journal Year: 2025, Volume and Issue: 93, P. 103046 - 103046

Published: May 17, 2025

The cerebral cortex is arguably the most complex organ in humans. cortical architecture characterized by a remarkable diversity of neuronal and glial cell types that make up its circuits. Following precise temporally ordered program, radial glia progenitor (RGP) cells generate all excitatory projection neurons cell-types. Cortical are produced either directly or via intermediate progenitors, through indirect neurogenesis. How extensive cell-type generated during development remains, however, fundamental open question. do RGPs quantitatively qualitatively neocortical neurons? does direct neurogenesis contribute to establishment lineage heterogeneity? Whether represent homogeneous and/or multipotent population, if consist heterogeneous groups currently also not known. In this review, we will summarize latest findings contributed deeper insight into above key questions.

Language: Английский

Citations

0
Higher-order thalamocortical circuits are specified by embryonic cortical progenitor types in the mouse brain DOI
Matthew J. Buchan, Gemma Gothard, Kashif Mahfooz

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(5), P. 114157 - 114157

Published: April 26, 2024

Language: Английский

Citations

1
Acute dietary methionine restriction highlights sensitivity of neocortex development to metabolic variations DOI Creative Commons
Sulov Saha,

Clémence Debacq,

Christophe Audouard

et al.

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

Published: Sept. 10, 2024

ABSTRACT Methionine -an essential amino acid that has to be provided by nutrition- and its metabolite S-Adenosyl methionine (SAM) are indispensable for cell proliferation, stem maintenance epigenetic regulation 1–5 , three processes central embryonic development 6 . Previous studies using chronic dietary restriction of methyl donors prior during gestation indicated (MR) is detrimental the or growth neocortex 7,8 however, consequences acute MR have not been extensively studied. Here, we designed a regime coinciding with neurogenic phases in mouse. Our results indicate 5 days leads severe reduction neuronal production. In comparison, liver heart was unaffected, highlighting an organ-specific response which also observed at cellular molecular levels. Progenitor cohort labeling revealed time-dependent sensitivity cycle analyses after MR, progenitors stalled S/G2 phases. Unexpectedly, induced completely rescued birth when switching dam back control diet remaining gestation, uncovering mechanism catch-up growth. Using multiplexed imaging probed metabolic markers following show pyruvate metabolism rewired progenitors. Altogether, our data uncover transient state quiescence G2/S metabolically distinct from G0 associated efficient More globally, study highlights both extreme developing changes remarkable plasticity.

Language: Английский

Citations

1
Advanced Techniques Using In Vivo Electroporation to Study the Molecular Mechanisms of Cerebral Development Disorders DOI Open Access

Yang Chen,

Atsunori Shitamukai, Shucai Yang

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(18), P. 14128 - 14128

Published: Sept. 15, 2023

The mammalian cerebral cortex undergoes a strictly regulated developmental process. Detailed in situ visualizations, imaging of these dynamic processes, and vivo functional gene studies significantly enhance our understanding brain development related disorders. This review introduces basic techniques recent advancements electroporation for investigating the molecular mechanisms underlying diseases. In utero (IUE) is extensively used to visualize modify including forced expression pathological mutants human diseases; thus, this method can be establish animal disease models. advent advanced techniques, such as genome editing, de novo knockout, knock-in, epigenetic spatiotemporal regulation, has further expanded list investigative tools. These tools include iON switch precise control timing copy numbers exogenous genes TEMPO temporal effects genes. We also introduce iGONAD method, an improved editing via oviductal nucleic acid delivery approach, novel genome-editing technique that accelerated exploration. methods are expected provide valuable insights into conditions associated with

Language: Английский

Citations

1