Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage

The developmental origin of oligodendrocyte progenitors (OLPs) in the forebrain has been controversial. We now show, by Cre-lox fate mapping in transgenic mice, that the first OLPs originate in the medial ganglionic eminence (MGE) and anterior entopeduncular area (AEP) in the ventral forebrain. From there, they populate the entire embryonic telencephalon including the cerebral cortex before being joined by a second wave of OLPs from the lateral and/or caudal ganglionic eminences (LGE and CGE). Finally, a third wave arises within the postnatal cortex. When any one population is destroyed at source by the targeted expression of diphtheria toxin, the remaining cells take over and the mice survive and behave normally, with a normal complement of oligodendrocytes and myelin. Thus, functionally redundant populations of OLPs compete for space in the developing brain. Notably, the embryonic MGE- and AEP-derived population is eliminated during postnatal life, raising questions about the nature and purpose of the competition.     

The caudal ganglionic eminence is a source of distinct cortical and subcortical cell populations

During development, the mammalian ventral telencephalon is comprised of three major proliferative zones: the medial (MGE), lateral (LGE) and caudal (CGE) ganglionic eminences. Through gene expression studies, in vitro migration assays, genetic mutant analysis and in vivo fate mapping in mice, we found that the CGE is a progenitor region that is distinct from both the MGE and LGE. Notably, CGE cells showed a unique in vivo pattern of migration, and the CGE contributed cells to nuclei distinct from those populated by the MGE and LGE. Moreover, we report that the migratory fate of cells from the CGE is intrinsically determined by embryonic day 13.5 (E13.5). Together, these results provide the first insights into the development and fate of the CGE.     

A method for rapid gain-of-function studies in the mouse embryonic nervous system.

We used ultrasound image-guided injections of high-titer retroviral vectors to obtain widespread introduction of genes into the mouse nervous system in utero as early as embryonic day 8.5 (E8.5). The vectors used included internal promoters that substantially improved proviral gene expression in the ventricular zone of the brain. To demonstrate the utility of this system, we extended our previous work in vitro by infecting the telencephalon in vivo as early as E8. 5 with a virus expressing Sonic Hedgehog. Infected embryos showed gross morphological brain defects, as well as ectopic expression of ventral telencephalic markers characteristic of either the medial or lateral ganglionic eminences.     

The brain of the crossopterygian fish Latimeria chalumnae: A survey of its gross structure

Summary The macroscopic anatomy of the brain of the single surviving crossopterygian species Latimeria chalumnae is described and depicted. The brain of this fish is slender and elongated. The rhombencephalon is well developed; its ventricular aspect shows four longitudinally arranged ridges which roughly correspond to the functional zones of Herrick and Johnston. The cerebellum comprises two extremely large auriculae and an unpaired, evaginated corpus cerebelli. The mesencephalon is small and does not show any marked differentiation of its surface. In the diencephalon, ventricular sulci mark the boundaries between the epithalamus, dorsal thalamus, ventral thalamus and hypothalamus. The dorsal thalamus protrudes into the ventricular cavity. The telencephalon can be clearly divided into a dorsal pallium and a ventral subpallium. The pallium is represented by a thickened, solid body. It is partly covered by a membranous roof, which in the median plane constitutes an ependymal septum. The subpallium is thin-walled and clearly evaginated. This structure and the ventral part of the pallium enclose a distinct lateral ventricle. The olfactory bulbs are connected with the telencephalon proper by extremely long olfactory peduncles.Interestingly, the brain of Latimeria appears to have gross structural features in common with all major groups of fish, i.e. the Chondrichthyes or cartilaginous fishes, the Dipnoi or lung fishes and the Actinopterygii or ray-finned fishes. Thus, with respect to the shape of the rhombencephalon and of the vestibulolateral lobe of the cerebellum, Latimeria approaches the chondrichthyan condition; the mesencephalon, the diencephalon and the subpallial parts of the telencephalon share a number of features with their dipnoan homologues, whereas the corpus cerebelli, the pallium and the membranous parts of the telencephalon clearly resemble the corresponding structures in the actinopterygians. No special structural affinities to the amphibians were noticed.     

Differential expression of RARbeta isoforms in the mouse striatum during development: a gradient of RARbeta2 expression along the rostrocaudal axis.

The retinoic acid receptor RARbeta is highly expressed in the striatum of the ventral telencephalon. We studied the expression pattern of different RARbeta isoforms in the developing mouse striatum by in situ hybridization. We found a differential ontogeny of RARbeta2 and RARbeta1/3 in embryonic day (E) 13.5 lateral ganglionic eminence (striatal primordium). RARbeta2 mRNA was detected primarily in the rostral and ventromedial domains, whereas RARbeta1/3 mRNAs were enriched in the caudal and dorsolateral domains. Notably, by E16.5, a prominent decreasing gradient of RARbeta2 mRNA was present in the developing striatum along the rostrocaudal axis, i.e., RARbeta2 was expressed at higher levels in the rostral than the caudal striatum. No such gradient was found for RARbeta1/3 and RARbeta3 mRNAs. The rostrocaudal RARbeta2 gradient gradually disappeared postnatally and was absent in the adult striatum. The differential expression pattern of RARbeta isoforms in the developing striatum may provide an anatomical basis for differential gene regulation by RARbeta signaling.     

Characterization of neogenin-expressing neural progenitor populations and migrating neuroblasts in the embryonic mouse forebrain

Many studies have demonstrated a role for netrin-1-deleted in colorectal cancer (DCC) interactions in both axon guidance and neuronal migration. Neogenin, a member of the DCC receptor family, has recently been shown to be a chemorepulsive axon guidance receptor for the repulsive guidance molecule (RGM) family of guidance cues [Rajagopalan S, Deitinghoff L, Davis D, Conrad S, Skutella T, Chedotal A, Mueller B, Strittmatter S (2004) Neogenin mediates the action of repulsive guidance molecule. Nat Cell Biol 6:755-762]. Here we show that neogenin is present on neural progenitors, including neurogenic radial glia, in the embryonic mouse forebrain suggesting that neogenin expression is a hallmark of neural progenitor populations. Neogenin-positive progenitors were isolated from embryonic day 14.5 forebrain using flow cytometry and cultured as neurospheres. Neogenin-positive progenitors gave rise to neurospheres displaying a high proliferative and neurogenic potential. In contrast, neogenin-negative forebrain cells did not produce long-term neurosphere cultures and did not possess a significant neurogenic potential. These observations argue strongly for a role for neogenin in neural progenitor biology. In addition, we also observed neogenin on parvalbumin- and calbindin-positive interneuron neuroblasts that were migrating through the medial and lateral ganglionic eminences, suggesting a role for neogenin in tangential migration. Therefore, neogenin may be a multi-functional receptor regulating both progenitor activity and neuroblast migration in the embryonic forebrain.     

Projections of the olfactory bulb in an elasmobranch fish,Sphyrna tiburo: segregation of inputs in the telencephalon

We have previously shown that the morphological compartmentalization of the elasmobranch olfactory bulb is accompanied by a topographical arrangement of the primary olfactory projections onto the bulb. If this spatial arrangement is significant for the processing of the information, one would expect it to be preserved in the secondary olfactory centers of the telencephalon. In this paper, we describe the elasmobranch secondary projections from the olfactory bulb to the telencephalon, focusing on their spatial arrangements within the forebrain. Results show that the olfactory input onto the telencephalon are segregated. The medial olfactory tract projects rostrally onto the superficial layer of the dorsal pallium and onto the lateral pallium. The lateral olfactory tract projects caudally onto the lateral pallium, the striatum and the area superficialis basalis. Thus, the secondary olfactory projections are segregated within the telencephalon, with an overlapping of the secondary fibers in the main projection area, the lateral pallium.     

Projections of the olfactory bulb in an elasmobranch fish, Sphyrna tiburo: segregation of inputs in the telencephalon

We have previously shown that the morphological compartmentalization of the elasmobranch olfactory bulb is accompanied by a topographical arrangement of the primary olfactory projections onto the bulb. If this spatial arrangement is significant for the processing of the information, one would expect it to be preserved in the secondary olfactory centers of the telencephalon. In this paper, we describe the elasmobranch secondary projections from the olfactory bulb to the telencephalon, focusing on their spatial arrangements within the forebrain. Results show that the olfactory input onto the telencephalon are segregated. The medial olfactory tract projects rostrally onto the superficial layer of the dorsal pallium and onto the lateral pallium. The lateral olfactory tract projects caudally onto the lateral pallium, the striatum and the area superficialis basalis. Thus, the secondary olfactory projections are segregated within the telencephalon, with an overlapping of the secondary fibers in the main projection area, the lateral pallium.     

Regulatory roles of conserved intergenic domains in vertebrate Dlx bigene clusters

Dlx homeobox genes of vertebrates are generally arranged as three bigene clusters on distinct chromosomes. The Dlx1/Dlx2, Dlx5/Dlx6, and Dlx3/Dlx7 clusters likely originate from duplications of an ancestral Dlx gene pair. Overlaps in expression are often observed between genes from the different clusters. To determine if the overlaps are a result of the conservation of enhancer sequences between paralogous clusters, we compared the Dlx1/2 and the Dlx5/Dlx6 intergenic regions from human, mouse, zebrafish, and from two pufferfish, Spheroides nephelus and Takifugu rubripes. Conservation between all five vertebrates is limited to four sequences, two in Dlx1/Dlx2 and two in Dlx5/Dlx6. These noncoding sequences are >75% identical over a few hundred base pairs, even in distant vertebrates. However, when compared to each other, the four intergenic sequences show a much more limited similarity. Each intergenic sequence acts as an enhancer when tested in transgenic animals. Three of them are active in the forebrain with overlapping patterns despite their limited sequence similarity. The lack of sequence similarity between paralogous intergenic regions and the high degree of sequence conservation of orthologous enhancers suggest a rapid divergence of Dlx intergenic regions early in chordate/vertebrate evolution followed by fixation of cis-acting regulatory elements.     

Slit-Robo interactions during cortical development

Interneurons are an integral part of cortical neuronal circuits. During the past decade, numerous studies have shown that these cells, unlike their pyramidal counterparts that are derived from the neuroepithelium along the lumen of the lateral ventricles, are generated in the ganglionic eminences in the subpallium. They use tangential migratory paths to reach the cortex, guided by intrinsic and extrinsic cues. Evidence is now emerging which suggests that the family of Slit proteins, acting through Robo receptors, play a role not only in axon guidance in the developing forebrain, but also as guiding signals in the migration of cortical interneurons. Here we describe the patterns of expression of Slit and Robo at different stages of forebrain development and review the evidence in support of their role in cortical interneuron migration. Slit-Robo signal transduction mechanisms are also important during normal development in a number of systems in the body and in disease states, making them potential therapeutic targets for the treatment of neurological disorders and certain types of cancer.     

The distribution and cellular localization of glutamic acid decarboxylase-65 (GAD65) mRNA in the forebrain and midbrain of domestic chick

The distribution and cellular localization of GAD65 mRNA in the forebrain and midbrain of domestic chick were examined by in situ hybridization histochemistry with ³⁵[S]-UTP labeled cRNA probes, using film and emulsion autoradiography. Film autoradiograms showed intense GAD65 labeling in many structures of the basal telencephalon, such as the medial and lateral striatum, the septum, the olfactory tubercle, the lateral bed nucleus of the stria terminalis, and the intrapeduncular nucleus, while the pallial telencephalon showed only a low level of labeling. Emulsion-coated sections revealed that GAD65 mRNA-containing neurons were at least six times more abundant in striatum than pallium, with only a uniformly scattered subpopulation labeled in pallium, and that the vast majority of the large scattered projection neurons of globus pallidus were heavily labeled for GAD65. Prominent labeling was also evident in the nucleus taeniae and subpallial amygdala, but not in the arcopallium in film autoradiograms. Within the diencephalon, the hypothalamus was more GAD65-rich than the thalamus. Additional subtelencephalic cell groups showing prominent labeling included the thalamic reticular nucleus and ventral lateral geniculate nucleus of the diencephalon, the nucleus pretectalis, subpretectalis and spiriformis lateralis of the pretectum, and the magnocellular isthmic nucleus of the optic lobe. Tectal layers 9–10 were also rich in GAD65. These results further clarify GABAergic circuits of the avian forebrain and midbrain, and show them to closely resemble those in mammals.