Evidences for tangential migrations in Xenopus telencephalon: developmental patterns and cell tracking experiments

Extensive tangential cell migrations have been described in the developing mammalian, avian, and reptilian forebrain, and they are viewed as a powerful developmental mechanism to increase neuronal complexity in a given brain structure. Here, we report for the first time anatomical and cell tracking evidence for the presence of important migratory processes in the developing forebrain of the anamniote Xenopus laevis. Combining developmental gene expression patterns (Pax6, Nkx2.1, Isl1, Lhx5, Lhx9, and Dll3), neurotransmitter identity (GABA, NOS, ChAT), and connectivity information, several types of putative migratory cell populations and migration routes originating in the ventral pallium and the subpallium are proposed. By means of in vivo cell tracking experiments, pallio-subpallial and subpallio-pallial migrating neurons are visualized. Among them, populations of Nkx2.1(+) striatal interneurons and pallial GABAergic interneurons, which also express the migratory marker doublecortin, are identified. Finally, we find that these tangentially migrating pallial interneurons travel through an "isl1-free channel" that may guide their course through the subpallium. Our findings strongly suggest that the developing Xenopus telencephalon shares many similarities with amniotes in terms of neuronal specification and migrations. However, some differences are discussed, particularly with regard to the evolution of the pallium.     

Comparison of the mammalian and avian telencephalon from the perspective of gene expression data.

Pallial and subpallial morphological subdivisions of the mouse and chicken telencephalon were examined from the new perspective given by gene markers expressed in these territories during development. The rationale of this approach is that common gene expression patterns may underlie similar histogenetic specification and, consequently, comparable morphological nature. The nested expression domains of the genes Dlx-2 and Nkx-2.1 are characteristic for the subpallium (lateral and medial ganglionic eminences). Similar expression of these markers in parts of the mouse septum and amygdala suggests that such parts may be considered subpallial. The genes Pax-6, Tbr-1 and Emx-1 are expressed in the pallium. Complementary areas of the septum and amygdala shared expression of these genes, suggesting these are the pallial parts of these units. Differences in the relative topography of pallial marker genes also define different regions of the pallium, which can be partially traced into the amygdala. Importantly, there is evidence of a novel "ventral pallium" subdivision, which is a molecularly distinct pallial territory intercalated between the striatum and the lateral pallium. Its derivatives in the mouse apparently belong to the claustroamygdaloid complex. Chicken genes homologous sequence-wise to these mouse developmental genes are expressed in topologically comparable patterns during development. The avian subpallium -the paleostriatum- expresses Dlx-2 and Nkx-2.1; expression extends as well into the septum and anterior and medial parts of the archistriatum. The avian pallium expresses Pax-6, Tbr-1 and Emx-1 and also contains a distinct ventral pallium, formed by the neostriatum and ventral intermediate parts of the archistriatum. The lateral pallium comprises the hyperstriatum ventrale, overlying temporo-parieto-occipital corticoid layer and piriform cortex, plus dorsal intermediate and posterior archistriatum. The dorsal pallium includes the dorsal, intercalated and accessory hyperstriatum, plus the dorsolateral corticoid area. The medial pallium contains the hippocampus and parahippocampal area. A dorsal part of the septum shares pallial molecular markers. Gene markers thus suggest common sets of molecular developmental determinants in either pallial or subpallial domains of the mouse and chicken telencephalon, extending all the way from the posterior pole (amygdala) to the septum. Ventral pallial derivatives identified as claustroamygdaloid in the mouse correlate with avian neostriatum and parts of the archistriatum.     

Consciousness without cortex

Sensory consciousness — the awareness and ability to report subjective experiences — is a property of biological nervous systems that has evolved out of unconscious processing over hundreds of millions of years. From which brain structures and based on which mechanisms can conscious experience emerge? Based on the body of work in human and nonhuman primates, the emergence of consciousness is intimately associated with the workings of the mammalian cerebral cortex with its specific cell types and layered structure. However, recent neurophysiological recordings demonstrate a neuronal correlate of consciousness in the pallial endbrain of crows. These telencephalic integration centers in birds originate embryonically from other pallial territories, lack a layered architecture characteristic for the cerebral cortex, and exhibit independently evolved pallial cell types. This argues that the mammalian cerebral cortex is not a prerequisite for consciousness to emerge in all vertebrates. Rather, it seems that the anatomical and physiological principles of the telencephalic pallium offer this structure as a brain substrate for consciousness to evolve independently across vertebrate phylogeny.     

The temporal sequence of the mammalian neocortical neurogenetic program drives mediolateral pattern in the chick pallium

The six-layered neocortex permits complex information processing in all mammalian species. Because its homologous region (the pallium) in nonmammalian amniotes has a different architecture, the ability of neocortical progenitors to generate an orderly sequence of distinct cell types was thought to have arisen in the mammalian lineage. This study, however, shows that layer-specific neuron subtypes do exist in the chick pallium. Deep- and upper-layer neurons are not layered but are segregated in distinct mediolateral domains in vivo. Surprisingly, cultured chick neural progenitors produce multiple layer-specific neuronal subtypes in the same chronological sequence as seen in mammals. These results suggest that the temporal sequence of the neocortical neurogenetic program was already inherent in the last common ancestor of mammals and birds and that mammals use this conserved program to generate a uniformly layered neocortex, whereas birds impose spatial constraints on the sequence to pattern the pallium.     

The corticostriatal junction: a crucial region for forebrain development and evolution

Most parts of the brain are conserved across reptiles and birds (sauropsids) and mammals. Two major qualitative differences occur in the upper part, or pallium, of the telencephalon, the most rostral part of the brain. Mammals have a six-layered neocortex and also exhibit a different morphological organization in the lateral half, or sector, of their pallium than do sauropsids. These differences of lateral pallial construction may derive from small but crucial differences in migration patterns of neuronal precursors generated at or above the corner of the lateral ventricle, the corticostriatal junction (CS). Sauropsids have a large structure, the dorsal ventricular ridge, that is proliferated from this region, and its anterior part (ADVR) receives ascending projections from the dorsal thalamus. Mammals have multiple structures in this same region-the lateral part of neocortex, amygdala, and claustrum-endopiriform formation. We propose here that, as the degree of development of structures that form the deeper tier of the pallium varies across the stages of embryology and across phylogeny, mutations may have occurred during evolution at the origin of mammals that had profound consequences for the fate of neural populations generated in the region of the CS and its neighboring pallial germinal zone.     

Development and evolution of the pallium

The neocortex is the most representative and elaborated structure of the mammalian brain and is related to the achievement of complex cognitive capabilities, which are disturbed following malformation or lesion. Searching for the evolutionary origin of this structure continues to be one of the most important and challenging questions in comparative neurobiology. However, this is extremely difficult because of the highly divergent evolution of the pallium in different vertebrates, which has obscured the comparison. Herein, we review developmental neurobiology data for trying to understand the genetic factors that define and underlie the parcellation of homologous pallial subdivisions in different vertebrates. According to these data, the pallium in all tetrapods parcellates during development into four major histogenetic subdivisions, which are homologous as fields across species. The neocortex derives from the dorsal pallium and, as such, is only comparable to the sauropsidian dorsal pallium (avian hyperpallium and lizard/turtle dorsal cortex). We also tried to identify developmental changes in phylogeny that may be responsible of pallial divergent evolution. In particular, we point out to evolutionary differences regarding the cortical hem (an important signaling center for pallial patterning, that also is a source of Cajal–Retzius cells, which are involved in cortical lamination), which may be behind the distinct organization of the pallium in mammals and non-mammals. In addition, we mention recent data suggesting a correlation between the appearance and elaboration of the subventricular zone (a new germinative cell layer of the developing neocortex), and the evolution of novel cell layers (the supragranular layers) and interneuron subtypes. Finally, we comment on epigenetic factors that modulate the developmental programs, leading to changes in the formation of functional areas in the pallium (within some constraints).     

Thoughts on the development, structure and evolution of the mammalian and avian telencephalic pallium

Various lines of evidence suggest that the development and evolution of the mammalian isocortex cannot be easily explained without an understanding of correlative changes in surrounding areas of the telencephalic pallium and subpallium. These are close neighbours in a common morphogenetic field and are postulated as sources of some cortical neuron types (and even of whole cortical areas). There is equal need to explain relevant developmental evolutionary changes in the dorsal thalamus, the major source of afferent inputs to the telencephalon (to both the pallium and subpallium). The mammalian isocortex evolved within an initially small dorsal part of the pallium of vertebrates, surrounded by other pallial parts, including some with a non-cortical, nuclear structure. Nuclear pallial elements are markedly voluminous in reptiles and birds, where they build the dorsal ventricular ridge, or hypopallium, which has been recently divided molecularly and structurally into a lateral pallium and a ventral pallium. Afferent pallial connections are often simplified as consisting of thalamic fibres that project either to focal cell aggregates in the ventral pallium (predominant in reptiles and birds) or to corticoid areas in the dorsal pallium (predominant in mammals). Karten's hypothesis, put forward in 1969, on the formation of some isocortical areas postulates an embryonic translocation into the nascent isocortex of the ventropallial thalamorecipient foci and respective downstream ventropallial target populations, as specific layer IV, layers II- III, or layers V-VI neuron populations. This view is considered critically in the light of various recent data, contrasting with the alternative possibility of a parallel, separate evolution of the different pallial parts. The new scenario reveals as well a separately evolving tiered structure of the dorsal thalamus, some of whose parts receive input from midbrain sensory centres (collothalamic nuclei), whereas other parts receive oligosynaptic 'lemniscal' connections bypassing the midbrain (lemnothalamic nuclei). An ampler look into known hodological patterns from this viewpoint suggests that ancient collothalamic pathways, which target ventropallial foci, are largely conserved in mammals, while some emergent cortical connections can be established by means of new collaterals in some of these pathways. The lemnothalamic pathways, which typically target ancestrally the dorsopallial isocortex, show parallel increments of relative size and structural diversification of both the thalamic cell populations and the cortical recipient areas. The evolving lemnothalamic pathways may interact developmentally with collothalamic corticopetal collaterals in the modality-specific invasion of the emergent new areas of isocortex.     

Naturally occurring neuronal plasticity in visual wulst of the Baya weaver, Ploceus philippinus (Linnaeus, 1766)

The visual wulst (VW), the rostro-dorsal surface of the avian telencephalon extending from the midline to the lateral region of the brain, is a laminated “bulge” consisting in four histologically distinct rostro-caudally arranged laminae with a specific sequence: hyperpallium apicale, interstitial nucleus of hyperpallium apicale, hyperpallium intercalatum and hyperpallium densocellulare. The VW has been proposed to be the avian equivalent of the mammalian striate cortex. Various behavioral studies including lesion experiments have indicated the importance of the VW, which receives visual and/or auditory cues. We have investigated qualitatively and quantitatively the fascinating structural changes occurring in VW neurons of the seasonally breeding bird, Ploceus philippinus (Linnaeus, 1766). The Golgi method was used to study the seasonal fluctuations in the neuronal classes of the VW with regard to dendritic thickness, spine morphology and spine density during both the non-breeding and breeding periods of male Baya weaver birds. Significant variations in parameters studied among the various neuronal types located in the different well-demarcated regions of the VW are believed to contribute to the functional differences reported among the wulst regions. Thus, this study extends our view demonstrating naturally occurring neuronal plasticity in a seasonally dynamic avian brain of a bird that hones not only its learning and memorizing system but also its social and sexual system in preparation for the breeding season.     

Telencephalic sources of the afferents of the main olfactory bulb in the frog Rana temporaria

Following horseradish peroxidase iontophoretic application into the main olfactory bulb (MOB) retrograde neuronal labeling was examined in the telencephalon in the frog. Labeled neurons, the sources of the MOB afferents are found in the mitral cell layer of the contralateral MOB, pallial and some subpallial areas. Very heavy labeling is observed in the pars ventralis of the lateral pallium, and to a lesser extent in the medial pallium, pars dorsalis of the lateral pallium and in the dorsal pallium. In subpallium labeled neurons are found in the eminentia postolfactoria, the rostral part of the medial septal nucleus, and in the nucleus of the ventro-medial telencephalic wall, which is probably homologous to the nucleus of the diagonal band (Broca) of mammals. No labelled neurons were found in the caudal portion of the MOB granular layer, usually referred to as the anterior olfactory nucleus. The arrangement of the MOB centrifugal innervation in amphibians is discussed in comparison with that in mammals.     

Regulation of neural stem cell by bone morphogenetic protein (BMP) signaling during brain development

Neurogenesis is the process in which neurons are generated from neural stem/progenitor cells (NSCs/NPCs). It involves the proliferation and neuronal fate specification/differentiation of NSCs, as well as migration, maturation and functional integration of the neuronal progeny into neuronal network. NSCs exhibit the two essential properties of stem cells: self-renewal and multipotency. Contrary to previous dogma that neurogenesis happens only during development, it is generally accepted now that neurogenesis can take place throughout life in mammalian brains. This raises a new therapeutic potential of applying stem cell therapy for stroke, neurodegenerative diseases and other diseases. However, the maintenance and differentiation of NSCs/NPCs are tightly controlled by the extremely intricate molecular networks. Uncovering the underlying mechanisms that drive the differentiation, migration and maturation of specific neuronal lineages for use in regenerative medicine is, therefore, crucial for the application of stem cell for clinical therapy as well as for providing insight into the mechanisms of human neurogenesis. Here, we focus on the role of bone morphogenetic protein (BMP) signaling in NSCs during mammalian brain development.     

Cytoarchitecture and connectivity of the amphibian medial pallium.

We investigated the cytoarchitecture and connectivity of the medial pallium of amphibians by intracellular recording and biocytin labeling. The experiments were carried out in a whole-brain in vitro preparation in the painted frog, Discoglossus pictus. Four types of neurons with specific axonal projection patterns and position in the medial pallium are distinguished, three types with extratelencephalic and one type with only intratelencephalic projections. Our findings corroborate the assumption that the anuran medial pallium is homologous to the subiculum and Ammon's horn of the mammalian hippocampus at a gross level, while the specific axonal projection patterns differ. Due to the absence of hippocampal neurons with only intrinsic projections, there seems to be no portion homologous to the dentate gyrus.     

神经细胞迁移导向的分子机制

自１９世纪以来的研究表明,在胚胎发育期间和出生后,包括人在内的哺乳动物神经系统的大部分神经细胞（也许是所有神经细胞）都要经过一定距离的多运动才能抵达它们发挥功能的部位。这些细胞如何知道往哪个方向迁移呢？我们在分子水平对这个问题进行了研究。１９９９年发表的结果给出这样一个答案：脑内存在导向性分子,可以指导神经细胞的迁移方向,具体的发现是：一个叫Ｓｌｉｔ的分泌性蛋白南,对神经细胞有性作用,它的浓度梯度     

Receptor tyrosine kinase-dependent neural crest migration in response to differentially localized growth factors

How different neural crest derivatives differentiate in distinct embryonic locations in the vertebrate embryo is an intriguing issue. Many attempts have been made to understand the underlying mechanism of specific pathway choices made by migrating neural crest cells. In this speculative review we suggest a new mechanism for the regulation of neural crest cell migration patterns in avian and mammalian embryos, based on recent progress in understanding the expression and activity of receptor tyrosine kinases during embryogenesis. Distinct subpopulations of crest-derived cells express specific receptor tyrosine kinases while residing in a migration staging area. We postulate that the differential expression of receptor tyrosine kinases by specific subpopulations of neural crest cells allows them to respond to localized growth factor ligand activity in the embryo. Thus, the migration pathway taken by neural crest subpopulations is determined by their receptor tyrosine kinase response to the differential localization of their cognate ligand.     

Fezl is required for the birth and specification of corticospinal motor neurons

The molecular mechanisms controlling the differentiation of neural progenitors into distinct subtypes of neurons during neocortical development are unknown. Here, we report that Fezl is required for the specification of corticospinal motor neurons and other subcerebral projection neurons, which are absent from Fezl null mutant neocortex. There is neither an increase in cell death in Fezl(-/-) cortex nor abnormalities in migration, indicating that the absence of subcerebral projection neurons is due to a failure in fate specification. In striking contrast, other neuronal populations in the same and other cortical layers are born normally. Overexpression of Fezl results in excess production of subcerebral projection neurons and arrested migration of these neurons in the germinal zone. These data indicate that Fezl plays a central role in the specification of corticospinal motor neurons and other subcerebral projection neurons, controlling early decisions regarding lineage-specific differentiation from neural progenitors.     

Avian brains and a new understanding of vertebrate brain evolution

We believe that names have a powerful influence on the experiments we do and the way in which we think. For this reason, and in the light of new evidence about the function and evolution of the vertebrate brain, an international consortium of neuroscientists has reconsidered the traditional, 100-year-old terminology that is used to describe the avian cerebrum. Our current understanding of the avian brain - in particular the neocortex-like cognitive functions of the avian pallium - requires a new terminology that better reflects these functions and the homologies between avian and mammalian brains.     

Opposing effects of hypoxia on catecholaminergic locus coeruleus and hypocretin/orexin neurons in chick embryos

Terrestrial vertebrate embryos face a risk of low oxygen availability (hypoxia) that is especially great during their transition to air‐breathing. To better understand how fetal brains respond to hypoxia, we examined the effects of low oxygen availability on brain activity in late‐stage chick embryos (day 18 out of a 21‐day incubation period). Using cFos protein expression as a marker for neuronal activity, we focused on two specific, immunohistochemically identified cell groups known to play an important role in regulating adult brain states (sleep and waking): the noradrenergic neurons of the Locus Coeruleus (NA‐LC), and the Hypocretin/Orexin (H/O) neurons of the hypothalamus. cFos expression was also examined in the Pallium (the avian analog of the cerebral cortex). In adult mammalian brains, cFos expression changes in a coordinated way in these areas. In chick embryos, oxygen deprivation simultaneously activated NA‐LC while deactivating H/O‐producing neurons; it also increased cFos expression in the Pallium. Activity in one pallial primary sensory area was significantly related to NA‐LC activity. These data reveal that at least some of the same neural systems involved in brain‐state control in adults may play a central role in orchestrating prenatal hypoxic responses, and that these circuits may show different patterns of coordination than seen in adults. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 1030–1037, 2014