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![Brain size and modes of neurogenesis in the pallium of vertebrates. a Simplified phylogenetic tree of vertebrates with schematic drawings at scale of the brain of model species in cross section. Differences in brain size between model species are proportional to their relative encephalization quotient (brain-to-body mass ratio) [29, 236]. Red and gray areas correspond to the pallium and subpallium, respectively. For monotremes, marsupials and primates, only a portion of the telencephalon can be shown at scale due to differences in size. Black dashed boxes indicate the brain areas shown in the drawings at scale. b Schematic drawings of germinal layers and types of progenitor cells in the embryonic pallium of vertebrates. Background colors group the clades according to their germinal layers: green, only ventricular zone (VZ); blue, VZ + subventricular zone (SVZ); orange, VZ + inner SVZ (iSVZ) + outer SVZ (oSVZ). The relative abundance of progenitor cell types in each group is also represented. aRGC apical radial glia cell, IPC intermediate progenitor cell, bRGC basal radial glia cell](publication/336121009/figure/fig3/AS:941352212783153@1601447265689/Brain-size-and-modes-of-neurogenesis-in-the-pallium-of-vertebrates-a-Simplified.png)
Brain size and modes of neurogenesis in the pallium of vertebrates. a Simplified phylogenetic tree of vertebrates with schematic drawings at scale of the brain of model species in cross section. Differences in brain size between model species are proportional to their relative encephalization quotient (brain-to-body mass ratio) [29, 236]. Red and gray areas correspond to the pallium and subpallium, respectively. For monotremes, marsupials and primates, only a portion of the telencephalon can be shown at scale due to differences in size. Black dashed boxes indicate the brain areas shown in the drawings at scale. b Schematic drawings of germinal layers and types of progenitor cells in the embryonic pallium of vertebrates. Background colors group the clades according to their germinal layers: green, only ventricular zone (VZ); blue, VZ + subventricular zone (SVZ); orange, VZ + inner SVZ (iSVZ) + outer SVZ (oSVZ). The relative abundance of progenitor cell types in each group is also represented. aRGC apical radial glia cell, IPC intermediate progenitor cell, bRGC basal radial glia cell
Source publication
The cerebral cortex varies dramatically in size and complexity between amniotes due to differences in neuron number and composition. These differences emerge during embryonic development as a result of variations in neurogenesis, which are thought to recapitulate modifications occurred during evolution that culminated in the human neocortex. Here,...
Citations
... No significant differences in composition were found. e Simplified schematic demonstrating the arrangement of pallial zones, supported by our data and results, in representative coronal sections of the adult mouse (modified from ref.79) and cichlid forebrain resulting from the developmental processes of neural tube evagination and eversion, respectively. Selected cichlid and mouse 37 cell-type pairs shown on the right demonstrate significant transcriptional similarity and support a model of partial eversion 2 of the teleost pallium. ...
The telencephalon has undergone remarkable diversification and expansion throughout vertebrate evolution, exhibiting striking variations in structural and functional complexity. Nevertheless, fundamental features are shared across vertebrate taxa, such as the presence of distinct regions including the pallium, subpallium, and olfactory structures. Teleost fishes have a uniquely “everted” telencephalon, which has confounded comparisons of their brain regions to other vertebrates. Here we combine spatial transcriptomics and single nucleus RNA-sequencing to generate a spatially-resolved transcriptional atlas of the Mchenga conophorus cichlid fish telencephalon. We then compare cell-types and anatomical regions in the cichlid telencephalon with those in amphibians, reptiles, birds, and mammals. We uncover striking transcriptional similarities between cell-types in the fish telencephalon and subpallial, hippocampal, and cortical cell-types in tetrapods, and find support for partial eversion of the teleost telencephalon. Ultimately, our work lends new insights into the organization and evolution of conserved cell-types and regions in the vertebrate forebrain.
... However, depending on the brain region and species, APs can also generate neurons rather than BPs (a process called direct neurogenesis). The neurons thus generated delaminate from the VZ and migrate, through the intermediate zone (IZ), to the cortical plate (CP) (Cardenas et al., 2018;Cardenas and Borrell, 2020). The newborn BPs also delaminate from the VZ but migrate only to the SVZ, where, depending on the mammalian species, they undergo a varying degree of self-amplification, followed by the generation of neurons and later of macroglial cells (astrocytes and oligodendrocytes; a process called gliogenesis) (Kriegstein and Alvarez-Buylla, 2009;Taverna et al., 2014;Tabata, 2015;Ohtsuka and Kageyama, 2019;Clavreul et al., 2022). ...
The development of the neocortex involves an interplay between neural cells and the vasculature. However, little is known about this interplay at the ultrastructural level. To gain a 3D insight into the ultrastructure of the developing neocortex, we have analyzed the embryonic mouse neocortex by serial block-face scanning electron microscopy (SBF-SEM). In this study, we report a first set of findings that focus on the interaction of blood vessels, notably endothelial tip cells (ETCs), and the neural cells in this tissue. A key observation was that the processes of ETCs, located either in the ventricular zone (VZ) or subventricular zone (SVZ)/intermediate zone (IZ), can enter, traverse the cytoplasm, and even exit via deep plasma membrane invaginations of the host cells, including apical progenitors (APs), basal progenitors (BPs), and newborn neurons. More than half of the ETC processes were found to enter the neural cells. Striking examples of this ETC process “invasion” were (i) protrusions of apical progenitors or newborn basal progenitors into the ventricular lumen that contained an ETC process inside and (ii) ETC process-containing protrusions of neurons that penetrated other neurons. Our observations reveal a — so far unknown — complexity of the ETC–neural cell interaction.
... In direct neurogenesis (dNG), a RG undergoes asymmetric division in the ventricular zone (VZ) to self-renew as well as generate one neuronal progeny [13][14][15] . In indirect neurogenesis (iNG), RG asymmetric division produces an intermediate progenitor (IP), which moves to the subventricular zone (SVZ) and undergoes symmetric division to generate two neurons [16][17][18][19] . Postmitotic PNs then undergo radial migration into the cortex, guided by radial fibers of RGs attached to the pia surface 20 . ...
... Between the two modes of neurogenesis, whereas dNG is ubiquitous along the neural tube that generate the entire central nervous system, iNG is restricted to the telencephalon that gives rise to the forebrain, especially the cerebral cortex 16,18,19,[27][28][29][30][31][32] . Across evolution, while dNG originated before the dawn of vertebrates and has been conserved ever since, iNG emerged in amniotes and has expanded tremendously in mammals, driving the innovation of a six-layered neocortex 17,18,[33][34][35][36] . ...
... Between the two modes of neurogenesis, whereas dNG is ubiquitous along the neural tube that generate the entire central nervous system, iNG is restricted to the telencephalon that gives rise to the forebrain, especially the cerebral cortex 16,18,19,[27][28][29][30][31][32] . Across evolution, while dNG originated before the dawn of vertebrates and has been conserved ever since, iNG emerged in amniotes and has expanded tremendously in mammals, driving the innovation of a six-layered neocortex 17,18,[33][34][35][36] . Within the neocortex, whereas dNGs generate all major PN classes, iNG amplifies and diversifies PNs within each class 30 . ...
The cerebral cortex comprises diverse types of glutamatergic projection neurons (PNs) generated from radial glial progenitors (RGs) through either direct neurogenesis or indirect neurogenesis (iNG) via intermediate progenitors (IPs). A foundational concept in corticogenesis is the “inside-out” model whereby successive generations of PNs sequentially migrate to deep then progressively more superficial layers, but its biological significance remains unclear; and the role of iNG in this process is unknown. Using genetic strategies linking PN birth-dating to projection mapping in mice, we found that the laminar deployment of IP-derived PNs substantially deviate from an inside-out rule: PNs destined to non-consecutive layers are generated at the same time, and different PN types of the same layer are generated at non-contiguous times. The overarching scheme of iNG is the sequential specification and precise laminar deployment of projection-defined PN types, which may contribute to the orderly assembly of cortical output channels and processing streams.
HIGHLIGHTS
- Each IP is fate-restricted to generate a pair of near-identical PNs
- Corticogenesis involves the orderly generation of fate-restricted IP temporal cohorts
- IP temporal cohorts sequentially as well as concurrently specify multiple PN types
- The deployment of PN types to specific layers does not follow an inside-out order
... Since birds and mammals diverged from a last common stem-amniote 320 million years ago ( Fig. 1A; Hedges 2002), they evolved a profoundly distinct cellular arrangement as integrative structures from different territories of the embryonic pallium. Of the four original pallial territories (ventral, lateral, dorsal, and medial), birds evolved rather nuclear integration centers out of the ventral pallium, whereas the major integration center of mammals, the six-layered neocortex, develops from the embryonic dorsal pallium (Jarvis et al. 2005;Puelles 2017;Cárdenas and Borrell 2020;Striedter and Northcutt 2020;Nieder 2021b). ...
Categorization is crucial for behavioral flexibility because it enables animals to group stimuli into meaningful classes that can easily be generalized to new circumstances. A most abstract quantitative category is set size, the number of elements in a set. This review explores how categorical number representations are realized by the operations of excitatory and inhibitory neurons in associative telencephalic microcircuits in primates and songbirds. Despite the independent evolution of the primate prefrontal cortex and the avian nidopallium caudolaterale, the neuronal computations of these associative pallial circuits show surprising correspondence. Comparing cellular functions in distantly related taxa can inform about the evolutionary principles of circuit computations for cognition in distinctly but convergently realized brain structures.
... Contrary to mouse and rat, a major proportion of basal intermediate progenitors in primates is characterized by sustained expression of Pax6 and a high proliferate potential. This high abundance of proliferative BPs results in an expanded SVZ and a high neuronal output in primates, especially in human [12,18,31,33,35,44,95]. ...
Background
Neocortex development has been extensively studied in altricial rodents such as mouse and rat. Identification of alternative animal models along the “altricial-precocial” spectrum in order to better model and understand neocortex development is warranted. The Greater cane rat (GCR, Thyronomys swinderianus ) is an indigenous precocial African rodent. Although basic aspects of brain development in the GCR have been documented, detailed information on neocortex development including the occurrence and abundance of the distinct types of neural progenitor cells (NPCs) in the GCR are lacking.
Methods
GCR embryos and fetuses were obtained from timed pregnant dams between gestation days 50–140 and their neocortex was analyzed by immunofluorescence staining using characteristic marker proteins for NPCs, neurons and glia cells. Data were compared with existing data on closely related precocial and altricial species, i.e. guinea pig and dwarf rabbit.
Results
The primary sequence of neuro- and gliogenesis, and neuronal maturation is preserved in the prenatal GCR neocortex. We show that the GCR exhibits a relatively long period of cortical neurogenesis of 70 days. The subventricular zone becomes the major NPC pool during mid-end stages of neurogenesis with Pax6 + NPCs constituting the major basal progenitor subtype in the GCR neocortex. Whereas dendrite formation in the GCR cortical plate appears to initiate immediately after the onset of neurogenesis, major aspects of axon formation and maturation, and astrogenesis do not begin until mid-neurogenesis. Similar to the guinea pig, the GCR neocortex exhibits a high maturation status, containing neurons with well-developed dendrites and myelinated axons and astrocytes at birth, thus providing further evidence for the notion that a great proportion of neocortex growth and maturation in precocial mammals occurs before birth.
Conclusions
Together, this work has deepened our understanding of neocortex development of the GCR, of the timing and the cellular differences that regulate brain growth and development within the altricial–precocial spectrum and its suitability as a research model for neurodevelopmental studies. The timelines of brain development provided by this study may serve as empirical reference data and foundation in future studies in order to model and better understand neurodevelopment and associated alterations.
... The plethora of pr ojection neur on subtypes in the cerebral neocortex is generated during embryonic de v elopment by a transient pool of neural progenitor cells (NPCs) (reviewed in (1)(2)(3)). While the ultimately six-layered neocortex is one of the defining features of mammals, the numbers and ratios between subtypes are species-specific, and an increased complexity of this organization is generally accepted to hav e enab led heightened cogniti v e function in primates (4)(5)(6). Abnormalities in the positioning, morphology 2 Nucleic Acids Research, 2023 or numbers of cortical neuron subtypes often result in dev elopmental neuropsy chiatric disor ders that impair cogniti v e, sensory and motor functions (7)(8)(9). Ther efor e, unravelling how NPCs generate the correct numbers of the different pr ojection neur on subtypes is pivotal for understanding the de v elopment of both the healthy and the diseased neocortex. ...
The seat of higher-order cognitive abilities in mammals, the neocortex, is a complex structure, organized in several layers. The different subtypes of principal neurons are distributed in precise ratios and at specific positions in these layers and are generated by the same neural progenitor cells (NPCs), steered by a spatially and temporally specified combination of molecular cues that are incompletely understood. Recently, we discovered that an alternatively spliced isoform of the TrkC receptor lacking the kinase domain, TrkC-T1, is a determinant of the corticofugal projection neuron (CFuPN) fate. Here, we show that the finely tuned balance between TrkC-T1 and the better known, kinase domain-containing isoform, TrkC-TK+, is cell type-specific in the developing cortex and established through the antagonistic actions of two RNA-binding proteins, Srsf1 and Elavl1. Moreover, our data show that Srsf1 promotes the CFuPN fate and Elavl1 promotes the callosal projection neuron (CPN) fate in vivo via regulating the distinct ratios of TrkC-T1 to TrkC-TK+. Taken together, we connect spatio-temporal expression of Srsf1 and Elavl1 in the developing neocortex with the regulation of TrkC alternative splicing and transcript stability and neuronal fate choice, thus adding to the mechanistic and functional understanding of alternative splicing in vivo.
... Further in development, neurogenic mechanisms generate diverse cell types. Throughout the embryonic neural tube, direct neurogenesis is ubiquitous and generates neurons across vertebrates [Paridaen and Huttner, 2014;Cárdenas and Borrell, 2020]. However, in amniotes but more so in mammals, indirect neurogenesis in the telencephalon, mediated via intermediate progenitors, plays a critical role in contributing to the neuronal diversity [Nomura et al., 2016;Cárdenas et al., 2018]. ...
As the highest center of sensory processing, initiation and modulation of behaviour, the pallium has seen prominent changes during the course of vertebrate evolution, culminating in the emergence of the mammalian isocortex. The processes underlying this remarkable evolution have been a matter of debate for several centuries. Recent studies using modern techniques in a host of vertebrate species are beginning to reveal mechanistic principles underlying pallial evolution from the developmental, connectome, transcriptome, and cell type levels. We attempt here, to trace and reconstruct the evolution of pallium from an evo-devo perspective, focusing on two phylogenetic extremes in vertebrates - cyclostomes and mammals, while considering data from intercalated species. We conclude that two fundamental processes of evolutionary change - conservation and diversification of cell types, driven by functional demands, are the primary forces dictating the emergence of the diversity of pallial structures, and imbibing them with the ability to mediate and control the exceptional variety of motor behaviours across vertebrates.
... These findings suggest that appropriate Notch signaling supplementation in higher vertebrates might contribute to the evolution of specific tissues. The numerous and distinct roles of Notch signaling in vertebrates are facilitated by different combinations of ligands and receptors [60,61], interactions through additional signaling molecules [62,63] or addition of novel genes [58,59]. These events determine the predominant role of Notch signaling in the evolution of tissues and organs [64][65][66][67]. ...
The Notch pathway is an ancient, evolutionary conserved intercellular signaling mechanism that is involved in cell fate specification and proper embryonic development. The Jagged2 gene, which encodes a ligand for the Notch family of receptors, is expressed from the earliest stages of odontogenesis in epithelial cells that will later generate the enamel-producing ameloblasts. Homozygous Jagged2 mutant mice exhibit abnormal tooth morphology and impaired enamel deposition. Enamel composition and structure in mammals are tightly linked to the enamel organ that represents an evolutionary unit formed by distinct dental epithelial cell types. The physical cooperativity between Notch ligands and receptors suggests that Jagged2 deletion could alter the expression profile of Notch receptors, thus modifying the whole Notch signaling cascade in cells within the enamel organ. Indeed, both Notch1 and Notch2 expression are severely disturbed in the enamel organ of Jagged2 mutant teeth. It appears that the deregulation of the Notch signaling cascade reverts the evolutionary path generating dental structures more reminiscent of the enameloid of fishes rather than of mammalian enamel. Loss of interactions between Notch and Jagged proteins may initiate the suppression of complementary dental epithelial cell fates acquired during evolution. We propose that the increased number of Notch homologues in metazoa enabled incipient sister cell types to form and maintain distinctive cell fates within organs and tissues along evolution.
... Cortical development begins with neurogenesis from progenitors lining the embryonic cerebral ventricle wall, which undergoes two fundamental forms of cell division that give rise to all glutamatergic neurons. 1 In direct neurogenesis (dNG), a radial glial cell (RG) undergoes asymmetric division to self-renew as well as generate one neuronal progeny [2][3][4][5] ; in indirect neurogenesis (iNG), RG asymmetric division produces an intermediate progenitor (IP), which then undergoes symmetric division to generate two neurons. [6][7][8][9] Whereas dNG is ubiquitous along the neural tube that gives rise to the central nervous system, iNG is restricted to the telencephalon giving rise to the forebrain, especially the cerebral cortex. ...
... 8 Across evolution, while RGmediated dNG originated before the dawn of vertebrates and has been conserved ever since, IP-mediated iNG is thought to have emerged in the last common ancestors (LCAs) of amniotes and subsequently diverged along two different evolutionary paths. 1 Along the sauropsids clade, dNG has dominated neuronal production across different pallial structures, including the 3-layered dorsal cortex of extant non-avian reptiles and the pallia of most avian species; iNG has remained rudimentary in most sauropsids, only to expand in certain birds (corvids) where it drives increased neuron numbers and density in nuclear structures of their pallium. [10][11][12] By contrast, along the synapsids path, iNG has expanded tremendously, particularly in the dorsal pallium, and is thought to drive the evolutionary innovation of a six-layered neocortex (Ncx). ...
... Across the embryonic pallial subdivisions, the medial domain gives rise to the hippocampal formation, the dorsal domain to the Ncx, the lateral domain to the insular cortex (Ins) and claustrum (Cl), and the ventral domain to the piriform cortex (Pir) and the pallial amygdala. 1 Among these, the six-layered Ncx comprises hierarchically organized pyramidal neuron (PyN) classes, each containing multiple finer-grained molecular and projection-defined subtypes. 17,18 Within this hierarchy, the intratelencephalic (IT) class mediates myriad processing streams within the cerebral hemisphere (including ipsilateral and contralateral intracortical and striatal projections), and the extratelencephalic (ET) class mediates subcortical outputs, including pyramidal tract (PT) neurons that project to all subcortical targets and the corticothalamic (CT) neurons that exclusively target the thalamus. ...
Variations in size and complexity of the cerebral cortex result from differences in neuron number and composition, rooted in evolutionary changes in direct and indirect neurogenesis (dNG and iNG) that are mediated by radial glia and intermediate progenitors (IPs), respectively. How dNG and iNG differentially contribute to neuronal number, diversity, and connectivity are unknown. Establishing a genetic fate-mapping method to differentially visualize dNG and iNG in mice, we found that while both dNG and iNG contribute to all cortical structures, iNG contributes the largest relative proportions to the hippocampus and neocortex. Within the neocortex, whereas dNG generates all major glutamatergic projection neuron (PN) classes, iNG differentially amplifies and diversifies PNs within each class; the two pathways generate distinct PN types and assemble fine mosaics of lineage-based cortical subnetworks. Our results establish a ground-level lineage framework for understanding cortical development and evolution by linking foundational progenitor types and neurogenic pathways to PN types.
... many areas of exception and overlap. For example, the simple category of "radial glia" in the prenatal brain has, of late, been expanded and subdivided as different subclasses have been found across developmental stages and species [87,88]. Adult neural stem cells in the SVZ express glial fibrillary acidic protein (GFAP), which is also a historically well-established marker of most astrocytes [29,72], and a subset of quiescent neural stem cells lacks nestin [59]. ...
Suspension and imaging cytometry techniques that simultaneously measure hundreds of cellular features are powering a new era of cell biology and transforming our understanding of human tissues and tumors. However, a central challenge remains in learning the identities of unexpected or novel cell types. Cell identification rubrics that could assist trainees, whether human or machine, are not always rigorously defined, vary greatly by field, and differentially rely on cell intrinsic measurements, cell extrinsic tissue measurements, or external contextual information such as clinical outcomes. This challenge is especially acute in the context of tumors, where cells aberrantly express developmental programs that are normally time, location, or cell-type restricted. Well-established fields have contrasting practices for cell identity that have emerged from convention and convenience as much as design. For example, early immunology focused on identifying minimal sets of protein features that mark individual, functionally distinct cells. In neuroscience, features including morphology, development, and anatomical location were typical starting points for defining cell types. Both immunology and neuroscience now aim to link standardized measurements of protein or RNA to informative cell functions such as electrophysiology, connectivity, lineage potential, phospho-protein signaling, cell suppression, and tumor cell killing ability. The expansion of automated, machine-driven methods for learning cell identity has further created an urgent need for a harmonized framework for distinguishing cell identity across fields and technology platforms. Here, we compare practices in the fields of immunology and neuroscience, highlight concepts from each that might work well in the other, and propose ways to implement these ideas to study neural and immune cell interactions in brain tumors and associated model systems.
