Orchestrated freedom: new insights into cortical neurogenesis

Llorca, Alfredo; Marı́n, Oscar

doi:10.1016/j.conb.2020.09.004

Cited by 16 publications

(16 citation statements)

References 85 publications

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“…In addition, intermediate progenitor cells (IPCs) are produced by asymmetric division, which then generate neurons by “indirect neurogenesis” through symmetric divisions in the subventricular zone (SVZ), where they re-locate after losing their apical and basal contacts ( Kriegstein and Alvarez-Buylla, 2009 ; Agirman et al, 2017 ; Borrell, 2019 ; Penisson et al, 2019 ). Further insights in generation and specification of neuronal progenitor cells as well as comprehensive aspects of neurogenesis have been widely described in several publications over the last years ( Taverna et al, 2014 ; Molnár et al, 2019 ; Kalebic and Huttner, 2020 ; Llorca and Marín, 2021 ). While it was initially suggested that indirect neurogenesis by IPCs mainly gives rise to upper-layer neurons ( Tarabykin et al, 2001 ; Nieto et al, 2004 ; Roy et al, 2004 ), recent studies by Cárdenas et al (2018) and Vitali et al (2018) propose indirect neurogenesis as major mode of producing neurons fated for the deep as well as superficial cortical layers during murine corticogenesis.…”

Section: Principles Of Neocortical Developmentmentioning

confidence: 99%

The Epigenome in Neurodevelopmental Disorders

Reichard

Zimmer-Bensch

2021

Front. Neurosci.

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Neurodevelopmental diseases (NDDs), such as autism spectrum disorders, epilepsy, and schizophrenia, are characterized by diverse facets of neurological and psychiatric symptoms, differing in etiology, onset and severity. Such symptoms include mental delay, cognitive and language impairments, or restrictions to adaptive and social behavior. Nevertheless, all have in common that critical milestones of brain development are disrupted, leading to functional deficits of the central nervous system and clinical manifestation in child- or adulthood. To approach how the different development-associated neuropathologies can occur and which risk factors or critical processes are involved in provoking higher susceptibility for such diseases, a detailed understanding of the mechanisms underlying proper brain formation is required. NDDs rely on deficits in neuronal identity, proportion or function, whereby a defective development of the cerebral cortex, the seat of higher cognitive functions, is implicated in numerous disorders. Such deficits can be provoked by genetic and environmental factors during corticogenesis. Thereby, epigenetic mechanisms can act as an interface between external stimuli and the genome, since they are known to be responsive to external stimuli also in cortical neurons. In line with that, DNA methylation, histone modifications/variants, ATP-dependent chromatin remodeling, as well as regulatory non-coding RNAs regulate diverse aspects of neuronal development, and alterations in epigenomic marks have been associated with NDDs of varying phenotypes. Here, we provide an overview of essential steps of mammalian corticogenesis, and discuss the role of epigenetic mechanisms assumed to contribute to pathophysiological aspects of NDDs, when being disrupted.

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Section: Principles Of Neocortical Developmentmentioning

confidence: 99%

The Epigenome in Neurodevelopmental Disorders

Reichard

Zimmer-Bensch

2021

Front. Neurosci.

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“…Future studies can investigate the mechanisms guiding interneurons of the same subclass to invade the same versus different brain regions and how they become specialized in each region. For glutamatergic progenitors, local cues modify several of their features and are thought to adapt them for region-specific architectures (Llorca and Marin, 2021). While glutamatergic progenitors vary across cortical regions (Bhaduri et al, 2021), how this variation is reflected in progenitors fated to produce the same subclass remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Cell-type specific transcriptomic signatures of neocortical circuit organization and their relevance to autism

Moussa

Wester

2022

Preprint

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A prevailing challenge in neuroscience is understanding how diverse neuronal cell types select their synaptic partners to form circuits. In the neocortex, major subclasses of excitatory projection neurons and inhibitory interneurons are conserved across functionally distinct regions. There is evidence these subclasses form circuits that depend primarily on their identity; however, regional cues likely also influence their choice of synaptic partners. We mined the Allen Brain Institute's single-cell RNA-sequencing database of mouse cortical neurons to study the expression of cellular adhesion molecules (CAMs) necessary for synapse formation in two regions: the anterior lateral motor cortex (ALM) and the primary visual cortex (VISp). We used the Allen's metadata to parse cells by clusters representing major excitatory and inhibitory subclasses that are common to both ALM and VISp. We then performed two types of pairwise differential gene expression analysis: 1) between different neuronal subclasses within the same brain region (ALM or VISp), and 2) between the same neuronal subclass in ALM and VISp. We filtered our results for differentially expressed genes encoding CAMs and developed a novel bioinformatic approach to determine the sets uniquely enriched in each neuronal subclass in ALM, VISp, or both. This analysis provides an organized set of genes that may regulate circuit formation in a cell-type specific manner. Furthermore, it identifies candidate mechanisms for the formation of circuits that are conserved across functionally distinct cortical regions or that are region dependent. Finally, we used the SFARI Human Gene Module to identify CAMs from our analysis that are related to risk for autism spectrum disorder (ASD). From over 3,000 differentially expressed genes, we found 40 ASD-associated CAMs that are enriched in specific neuronal subclasses in both ALM and VISp. Our analysis provides clear molecular targets for future studies to understand neocortical circuit organization and abnormalities that underly autistic phenotypes.

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“…In fact, it has been proposed that radial glial progenitor cells progress through sequential windows of competence as development proceeds and are capable to generate specific neuron types during each of these competence windows. This model of neurogenesis is commonly known as a progressive restriction (Molyneaux et al, 2007 ; Greig et al, 2013 ; Oberst et al, 2019 ; Lin et al, 2021 ; Llorca and Marín, 2021 ). Whether subpallial progenitor cells use similar mechanisms to produce IN diversity remains unclear, but clear temporal biases in the production of different IN identities have been reported.…”

Section: Fate Specification Of Cortical Interneuronsmentioning

confidence: 99%

Origin, Development, and Synaptogenesis of Cortical Interneurons

Llorca

Deogracias

2022

Front. Neurosci.

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The mammalian cerebral cortex represents one of the most recent and astonishing inventions of nature, responsible of a large diversity of functions that range from sensory processing to high-order cognitive abilities, such as logical reasoning or language. Decades of dedicated study have contributed to our current understanding of this structure, both at structural and functional levels. A key feature of the neocortex is its outstanding richness in cell diversity, composed by multiple types of long-range projecting neurons and locally connecting interneurons. In this review, we will describe the great diversity of interneurons that constitute local neocortical circuits and summarize the mechanisms underlying their development and their assembly into functional networks.

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Orchestrated freedom: new insights into cortical neurogenesis

Cited by 16 publications

References 85 publications

The Epigenome in Neurodevelopmental Disorders

The Epigenome in Neurodevelopmental Disorders

Cell-type specific transcriptomic signatures of neocortical circuit organization and their relevance to autism

Origin, Development, and Synaptogenesis of Cortical Interneurons

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