Time in Neurogenesis: Conservation of the Developmental Formation of the Cerebellar Circuitry

Rueda-Alaña, Eneritz; García‐Moreno, Fernando

doi:10.1159/000519068

Cited by 15 publications

(12 citation statements)

References 55 publications

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“…Our analyses of the developing cerebellum support early spatiotemporal patterning of Purkinje and granule cell subtypes that contributes to the cellular organization in the adult. We found consensus subtypes for most neural cell types in the developing cerebellum and observed equivalent sequences and timings of cell type emergence in the three species, in line with the previously proposed conservation of the cerebellum's cellular architecture and developmental program across amniotes 4,50 . A notable exception is the significantly higher relative abundance of Purkinje cells during early fetal development in human.…”

Section: Discussionsupporting

confidence: 88%

Cellular development and evolution of the mammalian cerebellum

Sepp

Leiss

Sarropoulos

et al. 2021

Preprint

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The expansion of the neocortex, one of the hallmarks of mammalian evolution, was accompanied by an increase in the number of cerebellar neurons. However, little is known about the evolution of the cellular programs underlying cerebellum development in mammals. In this study, we generated single-nucleus RNA-sequencing data for ~400,000 cells to trace the development of the cerebellum from early neurogenesis to adulthood in human, mouse, and the marsupial opossum. Our cross-species analyses revealed that the cellular composition and differentiation dynamics throughout cerebellum development are largely conserved, except for human Purkinje cells. Global transcriptome profiles, conserved cell state markers, and gene expression trajectories across neuronal differentiation show that the cerebellar cell type-defining programs have been overall preserved for at least 160 million years. However, we also discovered differences. We identified 3,586 genes that either gained or lost expression in cerebellar cells in one of the species, and 541 genes that evolved new expression trajectories during neuronal differentiation. The potential functional relevance of these cross-species differences is highlighted by the diverged expression patterns of several human disease-associated genes. Altogether, our study reveals shared and lineage-specific programs governing the cellular development of the mammalian cerebellum, and expands our understanding of the evolution of mammalian organ development.

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Section: Discussionsupporting

confidence: 88%

Cellular development and evolution of the mammalian cerebellum

Sepp

Leiss

Sarropoulos

et al. 2021

Preprint

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“…This confirmed that the pulse-labeling was effective, as there was no remaining EdU mark in the progenitor cells days after the injection [ Fig. 2D-F , (Rueda-Alaña and García-Moreno, 2022)].…”

Section: Resultssupporting

confidence: 64%

BirthSeq, a new method to isolate and analyze dated cells from any tissue in vertebrates

Rueda-Alaña,

Grillo,

Vazquez

et al. 2023

Preprint

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Embryonic development is a complex and dynamic process that unfolds over time and involves the production of increasing numbers of cells, as well as the diversification of different cell types. The impact of developmental time on the formation of the central nervous system is well documented, with evidence showing that time plays a critical role in establishing the identity of neuronal subtypes. However, the study of how time translates into genetic instructions driving cell fate is limited by the scarcity of suitable experimental tools. We introduce BirthSeq, a new method for isolating and analyzing cells based on their birth date. This innovative technique allows for in vivo labeling of cells, isolation via FACS, and analysis using high-throughput techniques. We demonstrate the effectiveness of BirthSeq for single-cell RNA sequencing and novel spatially resolved transcriptomic approaches in brain development across three vertebrate species (mouse, chick, and gecko). Overall, BirthSeq provides a versatile tool for studying any tissue in any vertebrate organism, helping to fill the necessity in developmental biology research by targeting cells and their temporal cues.

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“…In part, the rule of the older gets richer suggests that ancient circuits -such as those in brainstem, related to autonomic animal functions and directly involved in the survival of the animal- are more influential in the network and more stable in evolution. As a crucial example, it has been recently demonstrated the deeply conserved neurogenic formation of the cerebellum in several species of vertebrates 43 , and its remarkable orchestrating hub role to impact epileptic brain dynamics 35 . On the other side of the spectrum, circuits related to associative tasks -more related to cognition and human-specific behaviour- are not necessarily conserved, appear later in neurogenesis.…”

Section: Discussionmentioning

confidence: 99%

Linking hubness, embryonic neurogenesis, transcriptomics and diseases in human brain networks

Diez

García-Moreno

Sainz

et al. 2022

Preprint

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Understanding the architectural principle that shapes the topology of the human connectome at its multiple spatial scales is a major challenge for systems neuroscience. This would provide key fundamental principles and a theory for browsing brain’s networks, to ultimately generate hypothesis and approach to which extent key structures might impact different brain pathologies. In this work, we propose the hypothesis that the centrality of the different brain nodes in the human connectome is a product of their embryogenic age, and accordingly, early-born nodes should display higher hubness, and viceversa for late-born nodes. We tested our hypothesis by identifying and segmenting eighteen macroregions with a well-known embryogenic age, over which we calculated nodes’ centrality in the structural and functional networks at different spatial resolutions. First, nodes’ structural centrality correlated with their embryogenic age, fully confirming our working hypothesis. However, at the functional level, distinct trends were found at different resolutions. Secondly, the difference in embryonic age between nodes inversely correlated with the probability of existence and the weights of the links. This indicated the presence of a temporal developmental gradient that shapes connectivity and where nodes connect more to nodes with a similar age. Finally, brain transcriptomic analysis revealed high association between embryonic age, structural-functional centrality and the expression of genes related to nervous system development and synapse regulation. Furthermore, the spatial expression of genes causally related to major neurological diseases was highly correlated with spatial maps of region centrality. Overall, these results support the hypothesis that the embryogenic age of brain regions shapes the topology of adult brain networks. Our results show two key principles, “preferential age attachment” and “older gets richer” on the wiring of the human brain, thus shedding new light on the relationship between brain development, transcriptomics, node centrality, and neurological diseases.

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Time in Neurogenesis: Conservation of the Developmental Formation of the Cerebellar Circuitry

Cited by 15 publications

References 55 publications

Cellular development and evolution of the mammalian cerebellum

Cellular development and evolution of the mammalian cerebellum

BirthSeq, a new method to isolate and analyze dated cells from any tissue in vertebrates

Linking hubness, embryonic neurogenesis, transcriptomics and diseases in human brain networks

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