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A new model solving discrepancies of homology in the current model. Frontal (A–D) and lateral (E–F) views of the anterior forebrain in mouse (A, C, E) and zebrafish (B, D, F). Frontal planes (A–D) represent embryonic brain sections showing both current (left) and new (right) models on the regional identity of the anterior forebrain. (A, B) The color code represents gene expression data in mouse (A) and zebrafish (B). In the current view (left side of the brain), the ventral limit of the telencephalon is often delineated by the expression of Dlx2 (arrowhead) or Foxg1 (arrow), but the two borders do not coincide (which is more prominent in the teleost brain). In the new model, regional boundaries are delineated by abutting differentiated neurons, and they do not necessarily correspond to the limit delineated by gene expression. (C, D) The color code represents proposed regional identity in mouse (C) and zebrafish (D). In the current model established in amniotes (left side of the brain in C), the preoptic area (PO) is considered to be a part of the subpallium due to the expression of Foxg1 or Dlx genes, and Otp-dependent neuroendocrine cells are considered to be located in the hypothalamus. While in teleosts, the area called the PO contains the otp-dependent neuroendocrine cells (left side of the brain in D). In the new model, the corresponding area is the optic recess region (ORR). Considering the Otp-positive area in mouse as the ORR solves the discrepancy of the homology of neuroendocrine cell population between amniotes and teleosts. (E, F) Lateral view of mature brain sections of mouse (E) and zebrafish (F), representing the new model on the regional identity of the anterior forebrain. The color code of each region is the same as C and D. The anterior commissure (ac) and postoptic commissure (poc) can be simple anatomical landmarks for the regional boundary.
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In the current model, the most anterior part of the forebrain (secondary prosencephalon) is subdivided into the telencephalon dorsally and the hypothalamus ventrally. Our recent study identified a new morphogenetic unit named the optic recess region (ORR) between the telencephalon and the hypothalamus. This modification of the forebrain regionaliza...
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... presence of ORR would be a common feature in vertebrates, although in amniotes, the ORR has been difficult to be identified due to its relatively small size compared to the enlarged telencephalon. Comparison of gene expression patterns suggests that the transcrip- tion factors we found in the zebrafish ORR (Foxg1, Dlx2, Otp, Sim, etc.) are expressed in the telencephalic stalk region in amniotes (Fig. 4A), including the optic stalk ( Marcus et al. 1999;Roy et al. ...
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... the ORR corresponds to the PO of the mature teleost brain. A structure named the PO is also present in tetrapods, but the tetrapod PO does not exactly correspond to the same domain as the teleost PO (Fig. 4C,D). When the new model is applied to the tetrapod brain, the ORR includes domains that have been considered to be the "subpallial PO", and a part of the alar hypothalamus (Fig. 4C), thus reconciling this previous ...
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... the ORR corresponds to the PO of the mature teleost brain. A structure named the PO is also present in tetrapods, but the tetrapod PO does not exactly correspond to the same domain as the teleost PO (Fig. 4C,D). When the new model is applied to the tetrapod brain, the ORR includes domains that have been considered to be the "subpallial PO", and a part of the alar hypothalamus (Fig. 4C), thus reconciling this previous ...
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... important point is that the boundaries drawn using a set of transcription factors (Foxg1, Dlxl2, Shh, Otp, etc.) that have been used as "regional markers" do not fit the regional boundary defined by the differentiated cells (Fig. 4A,B). Since homologous genes are expressed in a similar pattern between dif- ferent species, they are useful to identify homologous areas or cell populations. However, the gene expres- sion patterns cannot be used to define the regional boundaries accurately. This leads to a reassessment of the interpretation of the "genoarchitecture" of the developing brains (Puelles & Ferran 2012;Puelles et al. ...
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... new model of the forebrain regionalization also clarifies the homology of the Otp-dependent neuroen- docrine cell population ( Affaticati et al. 2015). In both amniotes and teleosts, several categories of neuroen- docrine cells regulating pituitary functions are located in the territory expressing the transcription factor Otp. Based on the neurochemical and gene expression data, they are suggested to be homologous, but in amniotes the area containing these neuroendocrine cells has been identified as the hypothalamus, whereas in teleosts they are located in the preoptic area (PO; Herget et al. 2014;Biran et al. 2015). In the new framework, these Otp-expressing neuroendocrine cells are located in the ORR, both in amniotes and in teleosts ( Fig. ...
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... new model of the forebrain regionalization also changes the definition of the hypothalamus in tetra- pods. In the prosomeric model, the hypothalamus is divided into the alar and basal parts (Figs 2B, 4C). As mentioned above, a part of the "alar hypothalamus" containing the neuroendocrine cells is now considered to be a part of the ORR (Fig. 4C-F), which leads to the reduction of the "hypothalamus proper" in tetra- ...
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... the neocortex homologue in non-mam- malian species has been a long-lasting question, as it relates to the evolution of cognition. The area func- tionally similar to the mammalian neocortex receiving thalamo-cortical-like inputs (gp-like) can be observed in different parts of the pallium of Osteichthyes (see slanted green lines in Fig. 6C), not necessarily in the presumable DP (central portion of the pallium as indicated in green in Fig. 4A). When observing the differential location of the gp-like areas across verte- brates, one can think that any pallial region could actually evolve properties similar to the mammalian ...
Citations
... Our developmental studies have shown that the telencephalon, hypothalamus, and sensory nuclei of teleosts [16][17][18][19][20] differ greatly from amniotes. Indeed, teleost brain organization appears to be much less conserved than previously thought. ...
... The dorsal part of the secondary prosencephalon, which includes the telencephalon and the dorso-rostral part of the optic recess region (ORR) 17,18 , was excised. This region was labeled "telencephalon" (Tel). ...
In mammals and birds, tool-using species are characterized by their relatively large telencephalon containing a higher proportion of total brain neurons compared to other species. Some teleost species in the wrasse family have evolved tool-using abilities. In this study, we compared the brains of tool-using wrasses with various teleost species. We show that in the tool-using wrasses, the telencephalon and the ventral part of the forebrain and midbrain are significantly enlarged compared to other teleost species but do not contain a larger proportion of cells. Instead, this size difference is due to large fiber tracts connecting the dorsal part of the telencephalon (pallium) to the inferior lobe, a ventral mesencephalic structure absent in amniotes. The high degree of connectivity between these structures in tool-using wrasses suggests that the inferior lobe could contribute to higher-order cognitive functions. We conclude that the evolution of non-telencephalic structures might have been key in the emergence of these cognitive functions in teleosts.
... The first line of evidence is based on evolution (Mueller and Wullimann, 2009;Mueller, 2011). There is a consensus that over the course of 450 million years, the morphology of the fish forebrain diverged from other vertebrates (Butler and Hodos, 2005;Yamamoto et al., 2017). In fish, what started as the rostral part of the neural tube underwent eversion to create what is now known as the telencephalon, whereas in other vertebrates, it underwent evagination to create the forebrain (Figueroa et al., 2023;Northcutt and Braford, 1980). ...
... 94 This involves several processes such as cell migration and neuronal differentiation, facilitating the separation of the forebrain into the telencephalon (cerebrum) and the diencephalon (thalamus, hypothalamus, epithalamus, and subthalamus). 95 In line with the finding on the P300 amplitude, a recent transcriptome-wide association study by our group suggests that early neurodevelopment may also influence mismatch negativity, another EEG measure associated with auditory change detection. 70 Moreover, the role of forebrain development in schizophrenia is supported by a study using human induced pluripotent stem cells (hiPSCs). ...
Background and hypothesis:
Endophenotypes can help to bridge the gap between psychosis and its genetic predispositions, but their underlying mechanisms remain largely unknown. This study aims to identify biological mechanisms that are relevant to the endophenotypes for psychosis, by partitioning polygenic risk scores into specific gene sets and testing their associations with endophenotypes.
Study design:
We computed polygenic risk scores for schizophrenia and bipolar disorder restricted to brain-related gene sets retrieved from public databases and previous publications. Three hundred and seventy-eight gene-set-specific polygenic risk scores were generated for 4506 participants. Seven endophenotypes were also measured in the sample. Linear mixed-effects models were fitted to test associations between each endophenotype and each gene-set-specific polygenic risk score.
Study results:
After correction for multiple testing, we found that a reduced P300 amplitude was associated with a higher schizophrenia polygenic risk score of the forebrain regionalization gene set (mean difference per SD increase in the polygenic risk score: -1.15 µV; 95% CI: -1.70 to -0.59 µV; P = 6 × 10-5). The schizophrenia polygenic risk score of forebrain regionalization also explained more variance of the P300 amplitude (R2 = 0.032) than other polygenic risk scores, including the genome-wide polygenic risk scores.
Conclusions:
Our finding on reduced P300 amplitudes suggests that certain genetic variants alter early brain development thereby increasing schizophrenia risk years later. Gene-set-specific polygenic risk scores are a useful tool to elucidate biological mechanisms of psychosis and endophenotypes, offering leads for experimental validation in cellular and animal models.
... The expression of these genes in combination with dopa decarboxylase (Ddc) serves as a marker to identify bona fide DA neurons (Flames and Hobert, 2011). Teleosts show both conserved and divergent anatomical locations of DA and NA neuronal groups when compared with mammals (Ekström et al., 1994;Meek, 1994;Stuesse et al., 1994;Kaslin and Panula, 2001;Rink and Wullimann, 2002;Ma, 2003;Ryu et al., 2007;Yamamoto et al., 2017). Among the conserved anatomical locations are the NA groups in the hindbrain, the retinal amacrine DA neurons, and the posterior tubercular DA neurons, which appear to be homologous to the A11 mammalian groups (Ryu et al., 2007). ...
Catecholaminergic neuron clusters are among the most conserved neuromodulatory systems in vertebrates, yet some clusters show significant evolutionary dynamics. Because of their disease relevance, special attention has been paid to mammalian midbrain dopaminergic systems, which have important functions in motor control, reward, motivation, and cognitive function. In contrast, midbrain dopaminergic neurons in teleosts were thought to be lost secondarily. Here, we generated a CRISPR/Cas9-based knock-in transgene at the th locus, which allows the expression of the Q-system transcription factor QF2 linked to the Tyrosine hydroxylase open reading frame by an E2A peptide. The QF2 knock-in allele still expresses Tyrosine hydroxylase in catecholaminergic neurons. Coexpression analysis of QF2 driven expression of QUAS fluorescent reporter transgenes and of th mRNA and Th protein revealed that essentially all reporter expressing cells also express Th/th. We also observed a small group of previously unidentified cells expressing the reporter gene in the midbrain and a larger group close to the midbrain–hindbrain boundary. However, we detected no expression of the catecholaminergic markers ddc, slc6a3, or dbh in these neurons, suggesting that they are not actively transmitting catecholamines. The identified neurons in the midbrain are located in a GABAergic territory. A coexpression analysis with anatomical markers revealed that Th-expressing neurons in the midbrain are located in the tegmentum and those close to the midbrain–hindbrain boundary are located in the hindbrain. Our data suggest that zebrafish may still have some evolutionary remnants of midbrain dopaminergic neurons.
... The telencephalon is an essential brain part for an animal's cognitive functions and is highly diverse in structure among vertebrates. The dorsal telencephalon, or the pallium, is divided into several distinct regions in mammals; for example, the cerebral neocortex in the mammalian dorsal pallium (MDP), the hippocampus in the mammalian medial pallium (MMP), and the basolateral amygdala in the mammalian lateral pallium (MLP) (Briscoe and Ragsdale, 2019;Yamamoto et al., 2007;Northcutt, 2011;Yamamoto et al., 2017). The MDP is characterized by a six-layered structure and by stereotypical projections from all sensory modalities. ...
The dorsal telencephalon (i.e. the pallium) exhibits high anatomical diversity across vertebrate classes. The non-mammalian dorsal pallium accommodates various compartmentalized structures among species. The developmental, functional, and evolutional diversity of the dorsal pallium remain unillustrated. Here, we analyzed the structure and epigenetic landscapes of cell lineages in the telencephalon of medaka fish (Oryzias latipes) that possesses a clearly delineated dorsal pallium (Dd2). We found that pallial anatomical regions, including Dd2, are formed by mutually exclusive clonal units, and that each pallium compartment exhibits a distinct epigenetic landscape. In particular, Dd2 possesses a unique open chromatin pattern that preferentially targets synaptic genes. Indeed, Dd2 shows a high density of synapses. Finally, we identified several transcription factors as candidate regulators. Taken together, we suggest that cell lineages are the basic components for the functional regionalization in the pallial anatomical compartments and that their changes have been the driving force for evolutionary diversity.
... Furthermore, the relationship between the cerebrospinal-containing-spaces and the preoptic area and hypothalamus is likewise not entirely new. The preoptic area and the anterior hypothalamus of amniotes have been classified as a morphogenetic unit, the optic recess region, which is centered around the optic recess [31]. The lack of a clear boundary between the preoptic area and the anterior hypothalamus fits with this idea. ...
The preoptic area and the hypothalamus are inextricably linked. Together, they represent an area of the forebrain that is essential for survival of the species. Observations in mammals have suggested a classification of these structures into four rostrocaudal areas and three mediolateral zones. Two species of crocodiles were investigated to determine if this scheme or a modification of it could be applied to these reptiles. The resulting classification identified three rostrocaudal areas based on their respective relationship to the ventricular system: preoptic, anterior, and tuberal and four mediolateral zones: ependyma, periventricular, medial, and lateral. This scheme avoided the cumbersome and complicated nomenclature that has traditionally been used for morphologic studies of these areas in other reptiles, including crocodiles. The present classification is simple, straightforward, and readily applicable to other reptiles.
... Tissues from the same region can be compared, not only between Chondrichthyes, but also between other species. Given their evolutionary position, phylogenetically located between jawless vertebrates and bony fishes [128], comparative studies between these groups can elucidate some of their evolutionary histories. With the objective of clarifying the evolution of the vertebrate phototransduction cascade, RNA from the eyes of hagfish-Eptatretus cirrhatus, lampreys-Geotria australis and Mordacia mordax, elasmobranchs-Chiloscyllium punctatum, Carcharhinus amblyrhynchos, and Neotrygon kuhlii, bony fish-Amia calva, and gar-Lepisosteus platyrhincus [129] were sequenced and revealed that elasmobranchs have similar mechanisms of phototransduction cascade as the bony fishes, using GNAT1 together with PDE6, unlike, agnathostome that only has GNAT1. ...
Chondrichthyes (including sharks, rays, and chimaeras) are a class of jawed cartilaginous fishes (with skeletons composed primarily of cartilage), with major relevance to the marine ecosystems and to humanity. However, cartilaginous fishes are facing various threatens, inflicting abrupt declines in their populations. Thus, critical assessment of available molecular genetic variation, particularly retrieved from Chondrichthyans' transcriptomic analyses, represents a major resource to foster genomics research in this ancient group of vertebrate species. Briefly, RNA-Seq involves the sequencing of RNA strands present on a target tissue, which can assist genome annotation and elucidate genetic features on species without a sequenced genome. The resulting information can unravel responses of an individual to environmental changes, evolutionary processes, and support the development of biomarkers. We scrutinized more than 800 RNA-Seq entries publicly available, and reviewed more than one decade of available transcriptomic knowledge in chondrichthyans. We conclude that chondrichthyans’ transcriptomics is a subject in early development, since not all the potential of this technology has been fully explored, namely their use to prospectively preserve these endangered species. Yet, the transcriptomic database provided findings on the vertebrates’ evolution, chondrichthyans’ physiology, morphology, and their biomedical potential, a trend likely to expand further in the future.
... 1.3 The nest in the animal world: extent, differences, evolution Occurrence of nesting behaviour across a simplified phylogenetic tree of animals, with a focus on fish taxa. Adapted from the phylogeny proposed by Yamamoto et al. (2017) and Semmens et al. (2016). Data on nesting occurrence was obtained from Hansell (2005). ...
Nests are widespread in the animal world and aim to protect the young from predation and adverse environmental conditions while being a privileged place to assess sexual selection. These nests, modifications of the habitat in which they are built, influence the environmental conditions and likely affect the communities and
ecological processes. Among the nesting species, the sea lamprey (Petromyzon marinus L.) is an anadromous, semelparous migratory fish, whose nests consist of a mound of coarse elements downstream a pit with a fine substrate. The thesis firstly describes the reproductive behaviour of the sea lamprey by studying the link between the nests and the individuals that built them. A Capture-Mark-Recapture protocol showed that males and females visited up to 10 and 7 nests respectively, and that nests could be built by either pairs or groups of up to 5 individuals, resulting in a clearly polygynandrous mating system. Data obtained during this individual monitoring was used to set up a model providing a population size estimate via a simple nest count, a model that can be easily adapted to other populations and used via an online application. Intrasexual competition and cooperative nest building, as well as the existence of potential alternative reproductive tactics, were monitored at the scale of a nest and of an entire spawning site. Video monitoring within nests showed equal individual contributions to both nest building and mating, although aggressions perpetrated by some males suggested a hierarchy. Experimental injection of eggs into recently built nests indicated that the interaction between variables related to habitat choice (current velocity) and habitat modification (slope between the lower and upper points in the nest) affected egg retention in the nest, a major aspect of egg survival. Measurements of the maintenance of river lamprey (Lampetra fluviatilis L.) eggs in a controlled environment showed a significant role of substrate size. Finally, the link between the nest and its ecosystem was described through the study of the macroinvertebrate communities occupying the different zones and several ecosystem processes. The habitat heterogeneity created by sea lamprey generated biological heterogeneity, with an increased invertebrate diversity in the nest compared to control sites. However, nutrient retention, chlorophyll accretion and litter degradation were not affected. The general objective of this thesis is thus a better understanding of a species whose ecology and place in the ecosystem remain poorly understood, although threatened in its native range while being invasive where introduced, through the use of a characteristic structure of its life cycle: the nest.
... H. Chen et al., 2011). This involves several processes such as cell migration and neuronal differentiation, facilitating the separation of the forebrain into the telencephalon (cerebrum) and the diencephalon (thalamus, hypothalamus, epithalamus, and subthalamus) (Yamamoto et al., 2017). Notably, the EMX1 gene in the forebrain regionalization gene set also reached genome-wide significance in the latest schizophrenia GWAS (Trubetskoy et al., 2022). ...
Despite breakthroughs made by genome-wide association studies (GWAS) in our understanding of psychosis, further research is still needed to characterise the effects of the genetic variants identified and clarify the neurobiological mechanisms underlying these associations. In this thesis, I aim to bridge these knowledge gaps by studying endophenotypes for psychosis, which are intermediate phenotypes associated with the genetics of psychosis that pinpoint abnormalities in a specific neurobiological domain. In Chapter 1, I conducted a meta-analysis on the N100 event-related potential, combining the results of a local family study and previous literature. I found reduced N100 amplitudes and prolonged N100 latencies in both patients with psychosis and their unaffected relatives compared to controls, suggesting that the N100 is a promising endophenotype. Further analysis of the local family study revealed that the N100 was associated with the CHRNA4 gene, indicating the potential involvement of nicotinic acetylcholine receptors in the N100. In Chapter 2, I computed gene-set specific polygenic risk scores for psychosis by stratifying polygenic risk scores into specific biological domains and tested their associations with established endophenotypes. I found that reduced P300 amplitudes were associated with abnormalities in early brain development in psychosis, supporting the neurodevelopmental hypothesis of schizophrenia. Finally, Chapter 3 involves a mixed-model GWAS on adolescent verbal memory as a psychosis endophenotype in a sample of diverse genetic ancestry. I found new evidence of a significant genetic correlation between schizophrenia and verbal memory in adolescents, consistent with previous observations in family studies. Furthermore, I discovered two genome-wide significant loci that influence verbal memory performance. In particular, the NSF gene identified by my GWAS is involved in synaptic neurotransmission and membrane fusion, and thus my data suggest it plays a role in verbal memory deficits in psychosis. This thesis integrates multiple research methods covering neurophysiology, cognition, and genomics to show how endophenotypes for psychosis can inform our understanding of its aetiology.
... Circle was plotted only if FDR is lower than 0.01. Axon guidance pathways are enriched with pallial clusters (OCR C9 & 12), Dd2 cluster (OCR C6), subpallial cluster (OCR C1, 3,4,5) and common cluster (OCR C14). On the other hand, synaptic genes are enriched in OCR C6. ...
The dorsal telencephalon (i.e. the pallium) exhibits high anatomical diversity across vertebrate classes. The mammalian dorsal pallium accommodates a six layered-structure, the neocortex, whereas the teleostean dorsal pallium possesses various compartmentalized structures among species. The development, function and evolution of the fish dorsal pallium remain unillustrated. Here, we analyzed the structure and epigenetic landscapes of cell lineages in the telencephalon of medaka fish (Oryzias latipes) which possesses a clearly delineated dorsal pallium (the Dd2 region). We found that different pallial regions, including Dd2, are formed by mutually exclusive clonal units, and that each pallium compartment exhibits a distinct epigenetic landscape. In particular, Dd2 possesses a unique open chromatin pattern that preferentially targets synapse-related genes. Indeed, Dd2 shows a high density of synapses, which might reflect strong plasticity. Finally, we identified several transcription factors as candidate regulators for the Dd2, which are partially shared with the human neocortex and hippocampus.
