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16 Schematic presentation of present conclusions about claustral-insular development and composition, including the redefined ventral, lateral, and dorsal pallial domains (VPall, LPall, DPall). VPall is defined by the olfactory cortex and the VPall migration stream (green), which contributes locally to the bed nucleus of the external capsule (BEC), ventral endopiriform nucleus (EPv) and olfactory (piriform; Pir) populations (light gray shade), and possibly also to some other cells dispersed among the large migrated dorsal endopiriform nucleus (EPd) nucleus. According to Bielle et al. (2005) there are ventropallial Cajal-Retzius cells that depart from the VPall domain subpially (small green arrow). Data from Teissier et al. (2010) revealed that some deep VPall cells move tangentially via a subventricular route into the neocortex, invading the cortical plate in a dispersed way (deep green arrows marked as "Pierani cells", referring to the principal investigator of this important investigation). On the other hand, the new LPall is defined by the histogenetic conjunction of the claustrum (CLsp, CLp), forming first a superficial stratum, but finally a deep nucleus, and the subsequently inside-out developed, six-layered structure of the insula (orange postmitotic elements coming out of the LPall progenitors; derivatives in darker gray shades). Various cell cohorts labeled similarly as the CL by the Nr4a2 marker exit the original primordium and invade radially or tangentially other pallial domains (black arrows). The subplate cells (layer 6b) seem to expand dorsally from the CLsp shortly after E12.5. The EPd separates ventrally from the CLp as of E14.5 and invades the subjacent subpiriform VPall in a rostrocaudal gradient, using the space not occupied by the EPv (caudally, the EPc does the same, separating partially from the CLc; not shown in the schema; see Figure 4.14). Other cells disperse superficially (radially) into the insular cortex, mainly in its granular and disgranular portions. Finally, a further Nr4a2-positive population migrates marginally into the neighboring parietal cortex (between E14.5 and E16.5), and ends up in the infragranular layers, where I suggest they be called Arimatsu cells (see citations in text). Cell populations in the VPall are further complemented via pallio-pallial marginal tangential migration by the DPall-originated Hirata signpost cells, first recognized by their immunoreaction with the lot1 antibody (Sato et al., 1998; Tomioka et al., 2000). Obviously, once the insula-claustrum complex is ascribed to LPall, the DPall definition is modified by loss of the insula, which formerly was thought to belong to it.
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The mammalian claustrum is a pallial nucleus embedded in the telencephalic white matter under the insula. It is a Cinderella-like anatomic entity, which is not well understood in many ways, but whose constancy suggests it performs an essential function. This embryological essay first discusses in detail the diverse historic conceptions about how it...
Citations
... The original collopallial field hypothesis was based on a handful of gene expression patterns (Molnár and Butler 2002), and it was formulated before the modern tetrapartite pallium model that is now commonly used. The modern concept of VPall (olfactory), LPall (claustro-insular), and DPall (neocortical) pallial sectors (Puelles 2014(Puelles , 2017 seems to have rendered obsolete these notions ar-ticulated in Puelles et al. (2000) and Molnár and Butler(2002) (Fig. 4).Altogether,thegeneralpresence of the claustrum in all extant mammalian taxa (excluding the uncertainty in monotremes), together with shared histochemical, molecular, cytoarchitectural, and hodological features, suggests that the claustrum was already present in the now extinct pan-mammalian common ancestor (Montiel et al. 2011;Puelles 2017;Suárez et al. 2018;Bruguier et al. 2020). We need much more detailed comparative lineage-tracing studies in this part of the brain to settle these issues. ...
Conscious perception in mammals depends on precise circuit connectivity between cerebral cortex and thalamus; the evolution and development of these structures are closely linked. During the wiring of reciprocal thalamus-cortex connections, thalamocortical axons (TCAs) first navigate forebrain regions that had undergone substantial evolutionary modifications. In particular, the organization of the pallial-subpallial boundary (PSPB) diverged significantly between mammals, reptiles, and birds. In mammals, transient cell populations in internal capsule and early corticofugal projections from subplate neurons closely interact with TCAs to guide pathfinding through ventral forebrain and PSPB crossing. Prior to thalamocortical axon arrival, cortical areas are initially patterned by intrinsic genetic factors. Thalamocortical axons then innervate cortex in a topographically organized manner to enable sensory input to refine cortical arealization. Here, we review the mechanisms underlying the guidance of thalamocortical axons across forebrain boundaries, the implications of PSPB evolution for thalamocortical axon pathfinding, and the reciprocal influence between thalamus and cortex during development.
... Given the important roles of the claustrum in higher cognitive functions and potential neuronal mechanisms underlying psychiatric diseases in humans, it is pivotal to understand where and when the claustrum cells originate and how the claustrum develops in the primate brain. Though a discrete claustrum can be found in all therian brains, the claustrum is separated from the insular cortex by extreme capsule in primates including humans but not in rodents (21,22). The endopiriform nucleus (En), a ventral adjacent nucleus in rodents, does not exist in primates (23). ...
... As of now, molecular biology and transcriptomic approaches identified a group of genes that are expressed in the claustrum, the subplate and deep layers of the insula (21,24). It is suggested that the claustrum may share its origin with the insula from lateral pallium (LPALL) (22,24). However, it is perplexing that in utero electroporation of LPALL with enhanced green fluorescent protein at the time of subplate neurogenesis labeled primarily the insular cortex, with no apparent claustrum labeling (24). ...
... For example, autoradiographic labeling ( 3 H-thymidine) studies performed on the mouse at early embryonic stages found mouse claustrum labeling as of E11, and finished neurogenesis at E13 (32,33). Similar experiments performed on rats observed that claustral populations are produced between E11.5 and E14.5 with a peak at E12.5 (22). The most recent study by Hoerder-Suabedissen (34) on neurogenesis of the claustrum in mice indicated that claustrum neurons were born at a short time window, E12.5 and neurons in En were born at E11.5. ...
Understanding the claustrum's functions has recently progressed thanks to new anatomical and behavioral studies in rodents, which suggest that it plays an important role in attention, salience detection, slow-wave generation, and neocortical network synchronization. Nevertheless, knowledge about the origin and development of the claustrum, especially in primates, is still limited. Here, we show that neurons of rhesus macaque claustrum primordium are generated between embryonic day E48 and E55 and express some neocortical molecular markers, such as NR4A2, SATB2, and SOX5. However, in the early stages, it lacks TBR1 expression, which separates it from other surrounding telencephalic structures. We also found that two waves of neurogenesis (E48 and E55) in the claustrum, corresponding to the birthdates of layers 6 and 5 of the insular cortex, establish a "core" and "shell" cytoarchitecture, which is potentially a basis for differential circuit formation and could influence information processing underlying higher cognitive functions of the claustrum. In addition, parvalbumin-positive interneurons are the dominant interneuron type in the claustrum in fetal macaque, and their maturation is independent of that in the overlaying neocortex. Finally, our study reveals that the claustrum is likely not a continuance of subplate neurons of the insular cortex, but an independent pallial region, suggesting its potentially unique role in cognitive control.
... CLA origin is another puzzling problem, and morphogenetic and neurochemical similarities led some authors to postulate a common origin for CLA and the insular cortex [15,16]; on the other hand, a subcortical origin has also been reported [17][18][19]. Furthermore, according to the hybrid ontogeny theory, CLA is considered as an intermediary between the cortical plate and corpus striatum [17]. ...
... According to Bruguier et al. [18], the claustral neuronal population is born first starting from the lateral pallium, then insular cells migrate radially through the CLA, occupying progressively more superficial positions; thus, IN development is linked to CLA. In line with this hypothesis, the minor differences of protein expression observed between CLA and IN seem to support their common origin in agreement with described morphogenetic and neurochemical similarities of these structures [15,16]. ...
The present study, employing a comparative proteomic approach, analyzes the protein profile of pig claustrum (CLA), putamen (PU), and insula (IN). Pig brain is an interesting model whose key translational features are its similarities with cortical and subcortical structures of human brain. A greater difference in protein spot expression was observed in CLA vs PU as compared to CLA vs IN. The deregulated proteins identified in CLA resulted to be deeply implicated in neurodegenerative (i.e., sirtuin 2, protein disulfide-isomerase 3, transketolase) and psychiatric (i.e., copine 3 and myelin basic protein) disorders in humans. Metascape analysis of differentially expressed proteins in CLA vs PU comparison suggested activation of the α-synuclein pathway and L1 recycling pathway corroborating the involvement of these anatomical structures in neurodegenerative diseases. The expression of calcium/calmodulin-dependent protein kinase and dihydropyrimidinase like 2, which are linked to these pathways, was validated using western blot analysis. Moreover, the protein data set of CLA vs PU comparison was analyzed by Ingenuity Pathways Analysis to obtain a prediction of most significant canonical pathways, upstream regulators, human diseases, and biological functions. Interestingly, inhibition of presenilin 1 (PSEN1) upstream regulator and activation of endocannabinoid neuronal synapse pathway were observed. In conclusion, this is the first study presenting an extensive proteomic analysis of pig CLA in comparison with adjacent areas, IN and PUT. These results reinforce the common origin of CLA and IN and suggest an interesting involvement of CLA in endocannabinoid circuitry, neurodegenerative, and psychiatric disorders in humans.
... Given the important roles of the claustrum in higher cognitive functions and potential neuronal mechanisms underlying psychiatric diseases in humans, it is pivotal to understand where and when the claustrum cells originate and how the claustrum develops in the primate brain. Though the claustrum exists in almost all vertebrate brains, in species other than primates it lacks homology with humans since the extreme capsule separating the claustrum from the insula cortex is only present in primates (21,22). The endopiriform nucleus, a ventral adjacent nucleus in rodents, does not exist in primates (23). ...
... As of now, molecular biology and transcriptomic approaches identified a group of genes that are expressed in the claustrum, the subplate and deep layers of the insula (21,24). It is suggested that the claustrum may share its origin with the insula from lateral pallium (LPALL) (22,24). However, it is perplexing that in utero electroporation of LPALL with EGFP at the time of subplate neurogenesis labeled primarily the insular cortex, with no apparent claustrum labeling (24). ...
... For example, autoradiographic labeling (H 3 -thymidine) studies performed on the mouse at early embryonic stages found mouse claustrum labeling as of E11, and finished neurogenesis at E13 (32,33). Similar experiments performed on rats observed that claustral populations are produced between E11.5 and E14.5 with a peak at E12.5 (22). ...
Understanding the claustrum’s functions has recently progressed thanks to new anatomical and behavioral studies in rodents, which suggest that it plays an important role in attention, salience detection, slow-wave generation, and neocortical network synchronization. Nevertheless, knowledge about the origin and development of the claustrum, especially in primates, is still limited. Here, we show that neurons of rhesus macaque claustrum primordium are generated between embryonic day E48 and E55 and express some neocortical molecular markers, such as NR4A2, SATB2, and SOX5. However, in the early stages, it lacks TBR1 expression, which separates it from other surrounding telencephalic structures. We also found that two waves of neurogenesis (E48 and E55) in the claustrum, corresponding to the birthdates of layers 6 and 5 of the insular cortex, establish a “core” and “shell” cytoarchitecture, which is potentially a basis for differential circuit formation and could influence information processing underlying higher cognitive functions of the claustrum. In addition, parvalbumin-positive interneurons are the dominant interneuron type in the claustrum in fetal macaque, and their maturation is independent of that in the overlaying neocortex. Finally, our study reveals that the claustrum is likely not a continuance of subplate neurons of the insular cortex, but an independent pallial region, suggesting its potentially unique role in cognitive control.
Significance Statement
The claustrum is believed to have a role in many high cognitive functions. However, the origin and development of this mysterious structure remain unknown, and the understanding of its relationship with the neocortex is ambiguous. Here we examined neuron origin and development of claustrum in rhesus macaque during the prenatal and postnatal periods. We found that the claustrum is formed as an independent telencephalic area as early as E55, and it seems not related to the subplate of the insula, although it shares some molecular characteristics with the neocortex. The claustrum excitatory neurons are generated sequentially around E48 and E55 and build a “core and shell” structure that may be a basic computing neuronal circuit unit underlying higher cognitive functions.
... Furthermore, developmental origins have been well described by the concept of the pallium's division into four distinct fundamental sectors, each of which produces characteristic derivatives (Puelles et al., 1999(Puelles et al., , 2000(Puelles et al., , 2013. The latest pallial model proposed that the CLA originates within the lateral pallium sector together with the insular cortex (Puelles, 2014;Puelles et al., 2016;Bruguier et al., 2020). Moreover, previous studies, solely based on the expression pattern of a CLA marker, have hypothesized that the CLA is transiently formed at the brain surface, and that the insular cortex neurons later migrate radially through the CLA anlage to reach the superficial region, while passively displacing the CLA into the final deeper position (Puelles, 2014;Puelles et al., 2016Puelles et al., , 2017Watson and Puelles, 2017). ...
... The latest pallial model proposed that the CLA originates within the lateral pallium sector together with the insular cortex (Puelles, 2014;Puelles et al., 2016;Bruguier et al., 2020). Moreover, previous studies, solely based on the expression pattern of a CLA marker, have hypothesized that the CLA is transiently formed at the brain surface, and that the insular cortex neurons later migrate radially through the CLA anlage to reach the superficial region, while passively displacing the CLA into the final deeper position (Puelles, 2014;Puelles et al., 2016Puelles et al., , 2017Watson and Puelles, 2017). In addition, CLA development is thought to be closely related to the development of the dorsal endopiriform nucleus (DEn), which lies ventrally to the CLA. ...
... In addition, CLA development is thought to be closely related to the development of the dorsal endopiriform nucleus (DEn), which lies ventrally to the CLA. One genoarchitectonic observation suggested that the DEn neurons originate jointly with the CLA within the lateral pallium sector, and soon tangentially invade the ventral pallium to take up a final position deep to the piriform cortex (Puelles, 2014;Bruguier et al., 2020). ...
The claustrum (CLA) is a cluster of neurons located between the insular cortex and striatum. Many studies have shown that the CLA plays an important role in higher brain function. Additionally, growing evidence suggests that CLA dysfunction is associated with neuropsychological symptoms. However, how the CLA is formed during development is not fully understood. In the present study, we analyzed the development of the CLA, especially focusing on the migration profiles of CLA neurons in mice of both sexes. First, we showed that CLA neurons were generated between embryonic day (E) 10.5 and E12.5, but mostly at E11.5. Next, we labeled CLA neurons born at E11.5 using the FlashTag technology and revealed that most neurons reached the brain surface by E13.5 but were distributed deep in the CLA one day later at E14.5. Time-lapse imaging of GFP-labeled cells revealed that some CLA neurons first migrated radially outward and then changed their direction inward after reaching the surface. Moreover, we demonstrated that Reelin signal is necessary for the appropriate distribution of CLA neurons. The switch from outward to "reversed" migration of developing CLA neurons is distinct from other migration modes, in which neurons typically migrate in a certain direction, which is, simply outward or inward. Future elucidation of the characteristics and precise molecular mechanisms of CLA development may provide insights into the unique cognitive functions of the CLA.
Significance Statement
The CLA plays an important role in higher brain function, and its dysfunction is associated with neuropsychological symptoms. Although psychiatric disorders are increasingly being understood as disorders of neurodevelopment, little is known about CLA development, including its neuronal migration profiles and underlying molecular mechanisms. Here, we investigated the migration profiles of CLA neurons during development and found that they migrated radially outward and then inward after reaching the surface. This switch in the migratory direction from outward to inward may be one of the brain's fundamental mechanisms of nuclear formation. Our findings enable us to investigate the relationship between CLA maldevelopment and dysfunction, which may facilitate understanding of the pathogenesis of some psychiatric disorders.
... Critically for the current study, we recently found aberrant claustrum microstructure in very pretermborn adults, with these changes being associated with preterm GA and cognitive performance in adulthood . As in the period of preterm birth, the claustrum development overlaps with transient cell populations, namely subplate neurons and preoligodendrocytes, particularly vulnerable to adverse events like hypoxia-ischemia and inflammation, which frequently co-occur with prematurity (Bruguier et al., 2020;McClendon et al., 2017;Puelles, 2014;Volpe, 2019), we suggested an early impairment of the claustrum in prematurity. The current study is testing this hypothesis. ...
... In more detail, the claustrum is a tiny gray matter region between the extreme and external capsule adjacent to insula, and striatum (Puelles, 2014). Although ignored for a long time, the last two decades of increasing neuroscientific research on the claustrum revealed its highly important role in basic forebrain functioning (Crick and Koch, 2005). ...
... However, we found a volume decrease in the likewise highly connected thalamus. One difference between the two structures is the cellular composition, e.g., the direct subplate neuron involvement in the immature claustrum (Bruguier et al., 2020;Puelles, 2014). It is speculation that this point might be critical. ...
The human claustrum is a gray matter structure in the white matter between insula and striatum. Previous analysis found altered claustrum microstructure in very preterm-born adults associated with lower cognitive performance. As the claustrum development is related to hypoxia-ischemia sensitive transient cell populations being at-risk in premature birth, we hypothesized that claustrum structure is already altered in preterm-born neonates.
We studied anatomical and diffusion-weighted MRIs of 83 preterm- and 83 term-born neonates at term-equivalent age. Additionally, claustrum development was analyzed both in a spectrum of 377 term-born neonates and longitudinally in 53 preterm-born subjects. Data was provided by the developing Human Connectome Project.
Claustrum development showed increasing volume, increasing fractional anisotropy (FA), and decreasing mean diffusivity (MD) around term both across term- and preterm-born neonates. Relative to term-born ones, preterm-born neonates had (i) increased absolute and relative claustrum volumes, both indicating increased cellular and/or extracellular matter and being in contrast to other subcortical gray matter regions of decreased volumes such as thalamus; (ii) lower claustrum FA and higher claustrum MD, pointing at increased extracellular matrix and impaired axonal integrity; and (iii) aberrant covariance between claustrum FA and MD, respectively, and that of distributed gray matter regions, hinting at relatively altered claustrum microstructure.
Results together demonstrate specifically aberrant claustrum structure in preterm-born neonates, suggesting altered claustrum development in prematurity, potentially relevant for later cognitive performance.
... We have demonstrated here that none of them can be used to demarcate the claustrum during the first 2 postnatal weeks. Nurr1 has previously been used at the transcriptomics level as a marker for adult claustrum cells (Niu et al. 2022), and when comparing claustrum in different species Wang et al. 2011;Puelles 2014;Binks et al. 2019), however, it is widely expressed in lateral cortex (Arimatsu et al. 2003;Hoerder-Suabedissen et al. 2009), and thus not one of the preferred claustrum labeling strategies in adult brains. There is, however, a particularly dense patch of Nurr1-immunoreactive cells evident in the claustrum. ...
The claustrum is known for its extensive connectivity with many other forebrain regions, but its elongated shape and deep location have made further study difficult. We have sought to understand when mouse claustrum neurons are born, where they are located in developing brains, and when they develop their widespread connections to the cortex. We established that a well-characterized parvalbumin plexus, which identifies the claustrum in adults, is only present from postnatal day (P) 21. A myeloarchitectonic outline of the claustrum can be derived from a triangular fiber arrangement from P15. A dense patch of Nurr1+ cells is present at its core and is already evident at birth. Bromodeoxyuridine birth dating of forebrain progenitors reveals that the majority of claustrum neurons are born during a narrow time window centered on embryonic day 12.5, which is later than the adjacent subplate and endopiriform nucleus. Retrograde tracing revealed that claustrum projections to anterior cingulate (ACA) and retrosplenial cortex (RSP) follow distinct developmental trajectories. Claustrum-ACA connectivity matures rapidly and reaches adult-like innervation density by P10, whereas claustrum-RSP innervation emerges later over a protracted time window. This work establishes the timeline of claustrum development and provides a framework for understanding how the claustrum is built and develops its unique connectivity.
... The earliest indication of a distinct pallial commissure in vertebrates comes from the African spotted lung sh, a basal member of the lobe-nned sh lineage , this ts well with that found in the case of Satb2 expression in our models (present results). However, in rodents it has been shown that, together with subplate cells, claustrum cells are the earliest to be born in the lateral pallium (Puelles 2014). In the case of Xenopus (we have no data on lung sh development), Satb2 expression in this pallial domain appears later than other pallial expressions (unpublished data). ...
Satb2 is a transcription factor with functional and regulatory mechanisms, and post-translational modifications highly conserved in mammals. However, although its distribution has been analyzed in the mouse brain, there are few data in other non-mammal models. Therefore, in the present study we have analyzed the immunolocalization of Satb2 in the brain of adult specimens of different models at key evolutionary points of vertebrate diversification, including representative species of sarcopterygians and actinopterygians. In addition, we used other neuronal markers of highly conserved populations in the vertebrate brain, such as catecholaminergic, serotonergic and Otp populations, involved in the specificity of certain brain areas. The neuroanatomical pattern of Satb2, interpreted according to the current prosomeric model, serves to identify brain regions and compare them among the studied species, and with previous reported data, mainly for amniotes. We identified that Satb2 expressions have similar topologies in the subpallium of models studied, whereas striking differences were found in the pallium between sarcopterygian and actinopterygian vertebrates. Only the turtle showed expression in the dorsal derivatives of the pallium, specifically in the dorsal cortex, only scattered in Xenopus , whereas the lateral derivatives of the pallium expressed Satb2 in sarcopterygians, but not in actinopterygians. In the medial amygdala, or homologous structures, all models expressed Satb2, but only tetrapods also co-expressed Otp, probably originating from the paraventricular hypothalamic region, since only in those models a minor population of Satb2/Otp cells was also detected. In the caudal telencephalon, all models showed significant expression in the preoptic area, including the acroterminal domain of this region, where Satb2-expressing cells were dopaminergic. In the alar hypothalamus, all models showed Satb2 in the subparaventricular area, whereas in the basal hypothalamus only sarcopterygians showed a significant population in the tuberal hypothalamus, doubly labeled with Otp only in lungfish. The diencephalon of sarcopterygians showed Satb2 labeling in the prethalamus, and only turtles and lungfish showed expression in the thalamus. At midbrain levels, the optic tectum housed scattered Satb2 cells exclusively in turtles, while the expression along the rostrocaudal reticular formation and parabrachial nucleus was a conserved feature of sarcopterygians. The neuroanatomical pattern of Satb2 revealed important differences between sarcopterygians and actinopterygians, and these divergences may be related to the distinct functional involvement of Satb2 in the acquisition of various neural phenotypes and in the establishment of connectivity of these cells.
... The earliest indication of a distinct pallial commissure in vertebrates comes from the African spotted lung sh, a basal member of the lobe-nned sh lineage , this ts well with that found in the case of Satb2 expression in our models (present results). However, in rodents it has been shown that, together with subplate cells, claustrum cells are the earliest to be born in the lateral pallium (Puelles 2014). In the case of Xenopus (we have no data on lung sh development), Satb2 expression in this pallial domain appears later than other pallial expressions (unpublished data). ...
Satb2 is a transcription factor with functional and regulatory mechanisms, and post-translational modifications highly conserved in mammals. However, although its distribution has been analyzed in the mouse brain, there are few data in other non-mammal models. Therefore, in the present study we have analyzed the immunolocalization of Satb2 in the brain of adult specimens of different models at key evolutionary points of vertebrate diversification, including representative species of sarcopterygians and actinopterygians. In addition, we used other neuronal markers of highly conserved populations in the vertebrate brain, such as catecholaminergic, serotonergic and Otp populations, involved in the specificity of certain brain areas. The neuroanatomical pattern of Satb2, interpreted according to the current prosomeric model, serves to identify brain regions and compare them among the studied species, and with previous reported data, mainly for amniotes. We identified that Satb2 expressions have similar topologies in the subpallium of models studied, whereas striking differences were found in the pallium between sarcopterygian and actinopterygian vertebrates. Only the turtle showed expression in the dorsal derivatives of the pallium, specifically in the dorsal cortex, only scattered in Xenopus , whereas the lateral derivatives of the pallium expressed Satb2 in sarcopterygians, but not in actinopterygians. In the medial amygdala, or homologous structures, all models expressed Satb2, but only tetrapods also co-expressed Otp, probably originating from the paraventricular hypothalamic region, since only in those models a minor population of Satb2/Otp cells was also detected. In the caudal telencephalon, all models showed significant expression in the preoptic area, including the acroterminal domain of this region, where Satb2-expressing cells were dopaminergic. In the alar hypothalamus, all models showed Satb2 in the subparaventricular area, whereas in the basal hypothalamus only sarcopterygians showed a significant population in the tuberal hypothalamus, doubly labeled with Otp only in lungfish. The diencephalon of sarcopterygians showed Satb2 labeling in the prethalamus, and only turtles and lungfish showed expression in the thalamus. At midbrain levels, the optic tectum housed scattered Satb2 cells exclusively in turtles, while the expression along the rostrocaudal reticular formation and parabrachial nucleus was a conserved feature of sarcopterygians. The neuroanatomical pattern of Satb2 revealed important differences between sarcopterygians and actinopterygians, and these divergences may be related to the distinct functional involvement of Satb2 in the acquisition of various neural phenotypes and in the establishment of connectivity of these cells.
... The earliest indication of a distinct pallial commissure in vertebrates comes from the African spotted lung sh, a basal member of the lobe-nned sh lineage , this ts well with that found in the case of Satb2 expression in our models (present results). However, in rodents it has been shown that, together with subplate cells, claustrum cells are the earliest to be born in the lateral pallium (Puelles 2014). In the case of Xenopus (we have no data on lung sh development), Satb2 expression in this pallial domain appears later than other pallial expressions (unpublished data). ...
Satb2 is a transcription factor with functional and regulatory mechanisms, and post-translational modifications highly conserved in mammals. However, although its distribution has been analyzed in the mouse brain, there are few data in other non-mammal models. Therefore, in the present study we have analyzed the immunolocalization of Satb2 in the brain of adult specimens of different models at key evolutionary points of vertebrate diversification, including representative species of sarcopterygians and actinopterygians. In addition, we used other neuronal markers of highly conserved populations in the vertebrate brain, such as catecholaminergic, serotonergic and Otp populations, involved in the specificity of certain brain areas. The neuroanatomical pattern of Satb2, interpreted according to the current prosomeric model, serves to identify brain regions and compare them among the studied species, and with previous reported data, mainly for amniotes. We identified that Satb2 expressions have similar topologies in the subpallium of models studied, whereas striking differences were found in the pallium between sarcopterygian and actinopterygian vertebrates. Only the turtle showed expression in the dorsal derivatives of the pallium, specifically in the dorsal cortex, only scattered in Xenopus , whereas the lateral derivatives of the pallium expressed Satb2 in sarcopterygians, but not in actinopterygians. In the medial amygdala, or homologous structures, all models expressed Satb2, but only tetrapods also co-expressed Otp, probably originating from the paraventricular hypothalamic region, since only in those models a minor population of Satb2/Otp cells was also detected. In the caudal telencephalon, all models showed significant expression in the preoptic area, including the acroterminal domain of this region, where Satb2-expressing cells were dopaminergic. In the alar hypothalamus, all models showed Satb2 in the subparaventricular area, whereas in the basal hypothalamus only sarcopterygians showed a significant population in the tuberal hypothalamus, doubly labeled with Otp only in lungfish. The diencephalon of sarcopterygians showed Satb2 labeling in the prethalamus, and only turtles and lungfish showed expression in the thalamus. At midbrain levels, the optic tectum housed scattered Satb2 cells exclusively in turtles, while the expression along the rostrocaudal reticular formation and parabrachial nucleus was a conserved feature of sarcopterygians. The neuroanatomical pattern of Satb2 revealed important differences between sarcopterygians and actinopterygians, and these divergences may be related to the distinct functional involvement of Satb2 in the acquisition of various neural phenotypes and in the establishment of connectivity of these cells.
