Independent control of neurogenesis and dorsoventral patterning by NKX2-2 DOI Creative Commons
Sumin Jang,

Elena Abarinov,

J. A. Dobkin

et al.

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

Published: Oct. 13, 2024

SUMMARY Human neurogenesis is disproportionately protracted, lasting >10 times longer than in mouse, allowing neural progenitors to undergo more rounds of self-renewing cell divisions and generate larger neuronal populations. In the human spinal cord, expansion motor neuron lineage achieved through a newly evolved progenitor domain called vpMN (ventral progenitor) that uniquely extends expands neurogenesis. This behavior vpMNs controlled by transcription factor NKX2-2, which co-expressed with classical (pMN) marker OLIG2. this study, we sought determine molecular basis NKX2-2-mediated extension We found NKX2-2 represses proneural gene NEUROG2 two distinct, Notch-independent mechanisms are respectively apparent rodent progenitors: rodents (and chick), Olig2 its tinman domain, leading loss Neurog2 expression. vpMNs, however, but not OLIG2 , thereby proceed, albeit delayed protracted manner. Interestingly, ectopic expression tinman-mutant Nkx2-2 mouse pMNs phenocopies repressing Our studies identify Notch- tinman-independent mode -mediated repression observed progenitors, normally masked chicks due ’s tinman-dependent .

Language: Английский

Emerging approaches to enhance human brain organoid physiology DOI Creative Commons
Anna Pagliaro, Benedetta Artegiani, Delilah Hendriks

et al.

Trends in Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Brain organoids are important 3D models for studying human brain development, disease, and evolution. To overcome some of the existing limitations that affect organoid quality, reproducibility, characteristics, in vivo resemblance, current efforts directed to improve their physiological relevance by exploring different, yet interconnected, routes. In this review, these approaches latest developments discussed, including stem cell optimization, refining morphogen administration strategies, altering extracellular matrix (ECM) niche, manipulating tissue architecture mimic morphogenesis. Additionally, strategies increase diversity enhance maturation, such as establishing co-cultures, assembloids, xenotransplantation, reviewed. We explore how various factors can be tuned intermingled speculate on future avenues towards even more physiologically-advanced organoids.

Language: Английский

Citations

0
Myelination across cortical hierarchies and depths in humans and macaques DOI Creative Commons
Monami Nishio, Xingyu Liu,

Allyson P. Mackey

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

Abstract Myelination is fundamental to brain function, enabling rapid neural communication and supporting neuroplasticity throughout the lifespan. While hierarchical patterns of myelin maturation across cortical surface are well-documented in humans, it remains unclear which features reflect evolutionarily conserved developmental processes versus human-characteristic adaptations. Moreover, laminar development primate surface, shapes hierarchies supports functions ranging from sensory integration network communication, has been largely unexplored. Using neuroimaging measure T1-weighted/T2-weighted ratio tissue contrast as a proxy for content, we systematically compared depth-dependent trajectories myelination humans macaques. We identified “inside-out” pattern, with deeper layers exhibiting steeper increases earlier plateaus than superficial layers. This organization followed gradient progressing early sensorimotor regions prolonged association areas. Humans exhibited markedly extended timeline both depths macaques, allowing postnatal plasticity entire hierarchy — motor processing higher-order networks. potential may facilitate shaping circuits through experience ways that support perceptual cognitive capabilities.

Language: Английский

Citations

0
A dyad of human-specific NBPF14 and NOTCH2NLB orchestrates cortical progenitor abundance crucial for human neocortex expansion DOI

Nesil Eşiyok,

Neringa Liutikaite, Christiane Haffner

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(13)

Published: March 26, 2025

We determined the roles of two coevolved and coexpressed human-specific genes, NBPF14 NOTCH2NLB , on abundance cortical progenitors that underlie evolutionary expansion neocortex, seat higher cognitive abilities in humans. Using automated microinjection into apical (APs) embryonic mouse neocortex electroporation APs chimpanzee cerebral organoids, we show promotes delamination AP progeny, by promoting oblique cleavage plane orientation during division, leading to increased key basal progenitor type, radial glia. In contrast, proliferation, pool. When expressed together, exert coordinated effects, resulting while maintaining self-renewal APs. Hence, these genes orchestrate behavior APs, lineages their a manner essential for human neocortex.

Language: Английский

Citations

0
The Principle of Cortical Development and Evolution DOI Creative Commons
Zhengang Yang

Neuroscience Bulletin, Journal Year: 2024, Volume and Issue: unknown

Published: July 18, 2024

Abstract Human’s robust cognitive abilities, including creativity and language, are made possible, at least in large part, by evolutionary changes to the cerebral cortex. This paper reviews biology evolution of mammalian cortical radial glial cells (primary neural stem cells) introduces concept that a genetically step wise process, based on core molecular pathway already use, is process has molded neurogenesis. The mechanism, which been identified our recent studies, extracellular signal-regulated kinase (ERK)-bone morphogenic protein 7 (BMP7)-GLI3 repressor form (GLI3R)-sonic hedgehog (SHH) positive feedback loop. Additionally, I propose basis for dwarfism, exemplified lissencephalic mouse originated from larger gyrencephalic ancestor, an increase SHH signaling glia, antagonizes ERK-BMP7 signaling. Finally, that: (1) not key regulator primate expansion folding; (2) human do generate neocortical interneurons; (3) human-specific genes may be essential most expansion. hope this review assists colleagues field, guiding research address gaps understanding development evolution.

Language: Английский

Citations

3
Mechanisms and purpose of lowered action potential firing threshold in fast-spiking interneurons in the human neocortex DOI

Emőke Bakos,

Ádám Tiszlavicz,

Viktor Szegedi

et al.

Published: Oct. 28, 2024

Abstract The mammalian brain exhibits various interspecies differences. Microanatomical and molecular differences in homologous neurons between species are best characterized the neocortical mantle, but purpose of these remains poorly understood. We performed whole-cell microelectrode recordings microanatomical analyses human fast-spiking parvalbumin (pvalb)-expressing interneurons tissue resected during surgery. Fast-spiking exhibited a lower action potential (AP) firing threshold humans than mice. Compared with mouse neurons, displayed an elongated axon initial segment (AIS), AIS was deficient low-voltage activated inhibitory Kv1 potassium channels. Contrarily, ion channels were prominent neurons. Computational interneuron model simulations revealed that human-type lowers AP shortens time lag for generation. Thus, supports fast in–fast out electrical circuit function pvalb which have electrically slow membrane kinetics somata. Teaser neocortex structural adaptations to shorten IN-OUT delay

Language: Английский

Citations

1
Molecular Lineages and Spatial Distributions of Subplate Neurons in the Human Fetal Cerebral Cortex DOI Creative Commons

Xueyu Guo,

Trevor Lee,

Jason Sun

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

Abstract The expansion of neural progenitors and production distinct neurons are crucial for architectural assembly formation connectivity in human brains. Subplate (SPNs) among the firstborn fetal cerebral cortex, play a critical role establishing intra‐ extracortical connections. However, little is known about SPN origin developmental lineages. In this study, spatial landscapes molecular trajectories SPNs cortices from gestational weeks (GW) 10 to 25 created by performing transcriptomics single‐cell RNA sequencing. Genes be evolutionarily human‐specific genes associated with extracellular matrices (ECMs) found maintain stable proportions subplate other neuronal types. Enriched ECM gene expression varies cortical regions, highest level frontal lobe This study reveals lineage specification cortices, highlights underpinnings neurogenesis early structural folding.

Language: Английский

Citations

1
Independent control of neurogenesis and dorsoventral patterning by NKX2-2 DOI Creative Commons
Sumin Jang,

Elena Abarinov,

J. A. Dobkin

et al.

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

Published: Oct. 13, 2024

SUMMARY Human neurogenesis is disproportionately protracted, lasting >10 times longer than in mouse, allowing neural progenitors to undergo more rounds of self-renewing cell divisions and generate larger neuronal populations. In the human spinal cord, expansion motor neuron lineage achieved through a newly evolved progenitor domain called vpMN (ventral progenitor) that uniquely extends expands neurogenesis. This behavior vpMNs controlled by transcription factor NKX2-2, which co-expressed with classical (pMN) marker OLIG2. this study, we sought determine molecular basis NKX2-2-mediated extension We found NKX2-2 represses proneural gene NEUROG2 two distinct, Notch-independent mechanisms are respectively apparent rodent progenitors: rodents (and chick), Olig2 its tinman domain, leading loss Neurog2 expression. vpMNs, however, but not OLIG2 , thereby proceed, albeit delayed protracted manner. Interestingly, ectopic expression tinman-mutant Nkx2-2 mouse pMNs phenocopies repressing Our studies identify Notch- tinman-independent mode -mediated repression observed progenitors, normally masked chicks due ’s tinman-dependent .

Language: Английский

Citations

0