Human neuronal maturation comes of age: cellular mechanisms and species differences

Wallace, Jenelle L.; Pollen, Alex A.

doi:10.1038/s41583-023-00760-3

Cited by 27 publications

(11 citation statements)

References 273 publications

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“…To investigate UBE3A and UBE3A-ATS in the prenatal macaque brain, we focused on the neocortex. The neocortex has undergone Frontiers in Neuroanatomy 10 frontiersin.org cortical layers, GD 100 during the neurogenesis of upper layers and the start of neuronal maturation in deep layers, and GD 151 toward the end of cortical synaptogenesis in all cortical layers (Wallace and Pollen, 2024). At GD 48, UBE3A staining was widespread across the cortical wall but most prominent at the interface of the marginal zone and the cortical plate and in the ventricular zone.…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, the well-studied ‘inside-out’ development of the neocortex provides the anatomical advantage of observing multiple developmental stages simultaneously across the cortical thickness. We studied three-time points: GD 48 during the neurogenesis of deep cortical layers, GD 100 during the neurogenesis of upper layers and the start of neuronal maturation in deep layers, and GD 151 toward the end of cortical synaptogenesis in all cortical layers ( Wallace and Pollen, 2024 ). At GD 48, UBE3A staining was widespread across the cortical wall but most prominent at the interface of the marginal zone and the cortical plate and in the ventricular zone.…”

Section: Resultsmentioning

confidence: 99%

“…Translating developmental data from animal models to humans presents challenges due to complex timing differences across species ( Wallace and Pollen, 2024 ). Determining exact equivalencies is difficult, as factors like cerebral growth, neurogenesis, and synaptogenesis vary.…”

Section: Discussionmentioning

confidence: 99%

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Regional and cellular organization of the autism-associated protein UBE3A/E6AP and its antisense transcript in the brain of the developing rhesus monkey

Gonzalez Ramirez,

Salvador,

Patel

et al. 2024

Front. Neuroanat.

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Angelman syndrome (AS) is a neurogenetic disorder caused by mutations or deletions in the maternally-inherited UBE3A allele, leading to a loss of UBE3A protein expression in neurons. The paternally-inherited UBE3A allele is epigenetically silenced in neurons during development by a noncoding transcript (UBE3A-ATS). The absence of neuronal UBE3A results in severe neurological symptoms, including speech and language impairments, intellectual disability, and seizures. While no cure exists, therapies aiming to restore UBE3A function—either by gene addition or by targeting UBE3A-ATS—are under development. Progress in developing these treatments relies heavily on inferences drawn from mouse studies about the function of UBE3A in the human brain. To aid translational efforts and to gain an understanding of UBE3A and UBE3A-ATS biology with greater relevance to human neurodevelopmental contexts, we investigated UBE3A and UBE3A-ATS expression in the developing brain of the rhesus macaque, a species that exhibits complex social behaviors, resembling aspects of human behavior to a greater degree than mice. Combining immunohistochemistry and in situ hybridization, we mapped UBE3A and UBE3A-ATS regional and cellular expression in normal prenatal, neonatal, and adolescent rhesus macaque brains. We show that key hallmarks of UBE3A biology, well-known in rodents, are also present in macaques, and suggest paternal UBE3A silencing in neurons—but not glial cells—in the macaque brain, with onset between gestational day 48 and 100. These findings support proposals that early-life, perhaps even prenatal, intervention is optimal for overcoming the maternal allele loss of UBE3A linked to AS.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Regional and cellular organization of the autism-associated protein UBE3A/E6AP and its antisense transcript in the brain of the developing rhesus monkey

Gonzalez Ramirez,

Salvador,

Patel

et al. 2024

Front. Neuroanat.

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“…Two experiments demonstrated ELS-cognitive effects mediated by alterations in expression of these genes. Subjects whose mothers experienced an earthquake during their second trimester showed atypically high methylation of the NR3C1 gene 38 years later which correlated strongly with tests of working memory (Wang et al 2022 ). The second trimester is a dynamic phase in the differentiation of thalamic glutamatergic neurons, the distribution of GABAergic neurons, and the onset of gliogenesis (Kim et al 2023 ).…”

Section: Effects Of Els On Reading Disability and Dyslexiamentioning

confidence: 91%

“…Fortunately, two strategic pathways have evolved to counter these stress-linked threats to a child's learning potential and safe and healthy childhood. Each produces phenotypic change resulting from the normal maturational variability of an ongoing evolutionary process (Wallace and Polien 2024). To lessen allostatic damage, such adaptations should engage autonomously when stress exceeds an individual's level of tolerance, guided by age, genetic makeup, and environmental history.…”

Section: Introductionmentioning

confidence: 99%

Early life stress, literacy and dyslexia: an evolutionary perspective

Kershner

2024

Brain Struct Funct

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Stress and learning co-evolved in parallel, with their interdependence critical to the survival of the species. Even today, the regulation of moderate levels of stress by the central autonomic network (CAN), especially during pre- and post-natal periods, facilitates biological adaptability and is an essential precursor for the cognitive requisites of learning to read. Reading is a remarkable evolutionary achievement of the human brain, mysteriously unusual, because it is not pre-wired with a genetic address to facilitate its acquisition. There is no gene for reading. The review suggests that reading co-opts a brain circuit centered in the left hemisphere ventral occipital cortex that evolved as a domain-general visual processor. Its adoption by reading depends on the CAN’s coordination of the learning and emotional requirements of learning to read at the metabolic, cellular, synaptic, and network levels. By stabilizing a child’s self-control and modulating the attention network’s inhibitory controls over the reading circuit, the CAN plays a key role in school readiness and learning to read. In addition, the review revealed two beneficial CAN evolutionary adjustments to early-life stress “overloads” that come with incidental costs of school under-performance and dyslexia. A short-term adaptation involving methylation of the FKBP5 and NR3C1 genes is a liability for academic achievement in primary school. The adaptation leading to dyslexia induces alterations in BDNF trafficking, promoting long-term adaptive fitness by protecting against excessive glucocorticoid toxicity but risks reading difficulties by disruptive signaling from the CAN to the attention networks and the reading circuit.

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