Early emergence of cortical interneuron diversity in the mouse embryo

Mi, Da; Li, Zhen; Lim, Lynette; Li, Mingfeng; Moissidis, Monika; Yang, Yifei; Gao, Tianliuyun; Hu, Xiaoming; Pratt, Thomas; Price, David J.; Šestan, Nenad; Marı́n, Oscar

doi:10.1126/science.aar6821

Cited by 232 publications

(251 citation statements)

References 42 publications

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“…However, it might be that the induced neurons did not reach the same stage of development as endogenous cells. Matching cell types across different developmental stages remains a complex challenge in neurobiology, as shown this year by two RNA-sequencing studies 8,9 . These highlighted the difficulty of recognizing the transcription factors that define specific cell types at early stages of neuronal development in the brain's cerebral cortex.…”

Section: Ly N E T T E L I M and O S C A R M A R í Nmentioning

confidence: 99%

More than one way to induce a neuron

Lim¹,

Marı́n²

2018

Nature

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Section: Ly N E T T E L I M and O S C A R M A R í Nmentioning

confidence: 99%

More than one way to induce a neuron

Lim¹,

Marı́n²

2018

Nature

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“…Subtype diversity arises from the interplay of intrinsic genetic programs and extrinsic cues but capturing the underlying mechanisms remains challenging. By profiling neurons across development with single-cell transcriptomics, one can trace cell fate trajectories based on gene expression signatures (Mayer et al 2018;Mi et al 2018;Clark et al 2019;Tiklová et al 2019;Trapnell et al 2014). These studies provide insights into the dynamics and complexity of differentiating neural tissues, including lineage relationships, intermediate progenitors, timelines of maturation and the emergence of subtype identities (Trapnell et al 2014;Saelens et al 2019).…”

Section: Introductionmentioning

confidence: 99%

Morphological pseudotime ordering and fate mapping reveals diversification of cerebellar inhibitory interneurons

Wang

Lefebvre

2020

Preprint

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Understanding how diverse neurons are assembled into circuits requires a framework for describing cell types and their developmental trajectories. Here, we combined genetic fate mapping and pseudo-temporal profiling to resolve the diversification of cerebellar inhibitory interneurons based on morphology. The molecular layer interneurons (MLIs) derive from a common progenitor but comprise a diverse population of dendritic-, somatic-, and axon initial segment-targeting interneurons. MLIs are classically divided into two types. However, their morphological heterogeneity suggests an alternate model of one continuously varying population. Through clustering and trajectory inference of 811 MLI reconstructions at maturity and during development, we show that MLIs divide into two discrete classes but also present significant within-class heterogeneity. Pseudotime trajectory mapping uncovered the emergence of distinct phenotypes during migration and axonogenesis, well before neurons reach their final positions. Our study illustrates the utility of quantitative single-cell methods to morphology for defining the diversification of neuronal subtypes. Figure 2. Morphological heterogeneity among MLIs. (A) Left: Immunostaining of MLIs (Parvalbumin, cyan) and PCs (co-labeled by Parvalbumin and Calbindin, cyan and red, respectively) show the ML space in which MLIs reside. PC somata are enveloped by BC axons (white arrowhead). Right: Inverted image of four fluorescently-labelled MLIs. The lower MLI (pink arrowhead) has canonical BC morphologies, including axonal basket terminals around the PC somata (asterisks). The two upper MLIs (teal arrowhead) have canonical SC morphologies and reside within the upper ML. The faintly labelled MLI (blue arrowhead) has SC morphologies but reside within the lower ML. (B) Reconstruction of canonical BC from panel A, with complete dendritic arbor traced in orange, and complete axonal arbor traced in blue. (C) Reconstruction of canonical SC from panel A (cell on far right). (D-F) Representative images of MLIs with mixtures of BC and SC characteristics. Top: inverted fluorescence image; Bottom: reconstruction with dendritic (orange) and axonal (blue) traces. (D) MLI located in the middle ML with SC dendritic features, and a long horizontal axon (arrow) with descending basket collaterals (asterisks). (E) MLI located in the lower ML with SC-like dendritic and axonal arbors. (F) MLI located in the upper ML with a long horizontal axon (arrow) and two descending axon collaterals with basket formations around PC somas (asterisks). All scale bars are 50 μm.

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“…The diversity among GABAergic cells is specified as early as progenitor stages in the ganglionic eminences, the embryonic regions that give rise to cortical inhibitory neurons 3,4 .…”

Section: Introductionmentioning

confidence: 99%

Hippocampal hub neurons maintain unique functional properties throughout their lifetime

Bocchio

Gouny

Angulo-Garcia

et al. 2019

Preprint

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The temporal embryonic origins of cortical GABA neurons are critical for their specialization. In the neonatal hippocampus, GABA cells born the earliest (ebGABAs) operate as 'hubs' by orchestrating neuronal dynamics. However, their fate remains largely unknown. To fill this gap, we have examined CA1 ebGABAs using a combination of electrophysiology, neurochemical analysis, optogenetic connectivity mapping as well as ex vivo and in vivo calcium imaging. We show that CA1 ebGABAs not only operate as hubs during development, but also maintain distinct morpho-physiological and connectivity profiles, including a bias for long-range targets and local excitatory inputs. In vivo, ebGABAs signal a variety of network states, including the activation of local CA1 assemblies. Hence, ebGABAs are specified from birth to ensure unique functions throughout their lifetime. In the adult brain, this may take the form of a long-range hub role through the coordination of cell assemblies across distant regions.

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Early emergence of cortical interneuron diversity in the mouse embryo

Cited by 232 publications

References 42 publications

More than one way to induce a neuron

More than one way to induce a neuron

Morphological pseudotime ordering and fate mapping reveals diversification of cerebellar inhibitory interneurons

Hippocampal hub neurons maintain unique functional properties throughout their lifetime

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