Conservation of neural progenitor identity and the emergence of neocortical neuronal diversity

Shohayeb, Belal; Muzar, Zukhrofi; Cooper, Helen

doi:10.1016/j.semcdb.2021.05.024

Cited by 9 publications

(10 citation statements)

References 92 publications

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“…Nevertheless, while this statement can be true in neurogenic niches ( Brown et al, 2003 ; but see below), it is not for the so-called “non-newly generated, immature” neurons of the cerebral cortex ( Gómez-Climent et al, 2008 ; Piumatti et al, 2018 ; Rotheneichner et al, 2018 ; La Rosa et al, 2020a ; see below). Recent techniques allowing to go far beyond the simple localization of cell markers, such as clonal lineage tracing and single-cell transcriptomic profiling, confirm the existence of remarkable heterogeneity in cell populations and across species ( Shohayeb et al, 2021 ; Franjic et al, 2022 ; Schmitz et al, 2022 ). Finally, a further kind of re-expression of immaturity molecules, in which neurons dedifferentiate to a pseudo-immature status (“dematuration”), has been shown to occur in aging, inflammation, and hyperexcitation ( Hagihara et al, 2019 ).…”

Section: Identifying the “Young” Neurons: A Tricky Taskmentioning

confidence: 99%

How Widespread Are the “Young” Neurons of the Mammalian Brain?

Ghibaudi

Bonfanti

2022

Front. Neurosci.

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After the discovery of adult neurogenesis (stem cell-driven production of new neuronal elements), it is conceivable to find young, undifferentiated neurons mixed with mature neurons in the neural networks of the adult mammalian brain. This “canonical” neurogenesis is restricted to small stem cell niches persisting from embryonic germinal layers, yet, the genesis of new neurons has also been reported in various parenchymal brain regions. Whichever the process involved, several populations of “young” neurons can be found at different locations of the brain. Across the years, further complexity emerged: (i) molecules of immaturity can also be expressed by non-dividing cells born during embryogenesis, then maintaining immature features later on; (ii) remarkable interspecies differences exist concerning the types, location, amount of undifferentiated neurons; (iii) re-expression of immaturity can occur in aging (dematuration). These twists are introducing a somewhat different definition of neurogenesis than normally assumed, in which our knowledge of the “young” neurons is less sharp. In this emerging complexity, there is a need for complete mapping of the different “types” of young neurons, considering their role in postnatal development, plasticity, functioning, and interspecies differences. Several important aspects are at stake: the possible role(s) that the young neurons may play in maintaining brain efficiency and in prevention/repair of neurological disorders; nonetheless, the correct translation of results obtained from laboratory rodents. Hence, the open question is: how many types of undifferentiated neurons do exist in the brain, and how widespread are they?

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Section: Identifying the “Young” Neurons: A Tricky Taskmentioning

confidence: 99%

How Widespread Are the “Young” Neurons of the Mammalian Brain?

Ghibaudi

Bonfanti

2022

Front. Neurosci.

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“…Ctx represents the cortex, RA is retinoic acid, SHH is sonic hedgehog and FGF is fibroblast growth factor. Black circles labeled (1) (Storm et al, 2006; Molotkova et al, 2007), (2) (Chatzi et al, 2011), (3) (Borello et al, 2008; Shohayeb et al, 2021), (4) (Su et al, 2022), (5) (Vogt et al, 2014) refer to previous findings. The red circle outline represents the findings of the current study.…”

Section: Supplementary Figuresmentioning

confidence: 94%

Spatial enhancer activation determines inhibitory neuron identity

Dvoretskova

Kittke

et al. 2023

Preprint

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The mammalian telencephalon contains a tremendous diversity of GABAergic projection neuron and interneuron types, that originate in a germinal zone of the embryonic basal ganglia. How genetic information in this transient structure is transformed into different cell types is not yet fully understood. Using a combination ofin vivolineage tracing, CRISPR perturbation and ChIP-seq in mice, we found that the transcription factor MEIS2 favors the development of projection neurons through genomic binding sites in regulatory enhancers of projection neuron specific genes. MEIS2 requires the presence of the homeodomain transcription factor DLX5 to direct its functional activity towards these sites. In interneurons, the activation of projection neuron specific enhancers by MEIS2 and DLX5 is repressed by the transcription factor LHX6. When MEIS2 carries a mutation associated with intellectual disability in humans, it is less effective at activating enhancers involved in projection neuron development. This suggests that GABAergic differentiation may be impaired in patients carrying this mutation. Our research has uncovered a mechanism by which the selective activation of enhancers plays a crucial role in the establishment of neuronal identity, as well as in potential pathological mechanisms.

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“…During embryonic development of the vertebrate brain, spatially distinct regions with specific cognitive and informationprocessing functions emerge. Underlying these different functions is the spatiotemporally controlled generation of the different types of neurons present in each brain region (Ge et al, 2022;Lodato & Arlotta, 2015;Shohayeb et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

A quantitative characterization of early neuron generation in the developing zebrafish telencephalon

Casas Gimeno,

Dvorianinova,

Lembke

et al. 2023

Developmental Neurobiology

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The adult brain is made up of anatomically and functionally distinct regions with specific neuronal compositions. At the root of this neuronal diversity are neural stem and progenitor cells (NPCs) that produce many neurons throughout embryonic development. During development, NPCs switch from initial expanding divisions to neurogenic divisions, which marks the onset of neurogenesis. Here, we aimed to understand when NPCs switch division modes to generate the first neurons in the anterior‐most part of the zebrafish brain, the telencephalon. To this end, we used the deep learning‐based segmentation method Cellpose and clonal analysis of individual NPCs to assess the production of neurons by NPCs in the first 24 h of zebrafish telencephalon development. Our results provide a quantitative atlas detailing the production of telencephalic neurons and NPC division modes between 14 and 24 h postfertilization. We find that within this timeframe, the switch to neurogenesis is gradual, with considerable heterogeneity in individual NPC neurogenic potential and division rates. This quantitative characterization of initial neurogenesis in the zebrafish telencephalon establishes a basis for future studies aimed at illuminating the molecular mechanisms and regulators of early neurogenesis.

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Conservation of neural progenitor identity and the emergence of neocortical neuronal diversity

Cited by 9 publications

References 92 publications

How Widespread Are the “Young” Neurons of the Mammalian Brain?

How Widespread Are the “Young” Neurons of the Mammalian Brain?

Spatial enhancer activation determines inhibitory neuron identity

A quantitative characterization of early neuron generation in the developing zebrafish telencephalon

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