Caudal Cortex Research Articles

Supraspinal gene transfer by intrathecal adeno-associated virus serotype 5.

We report the pattern of transgene expression across brain regions after intrathecal delivery of adeno-associated virus serotype 5 (AAV5). Labeling in hindbrain appeared to be primarily neuronal, and was detected in sensory nuclei of medulla, pontine nuclei, and all layers of cerebellar cortex. Expression in midbrain was minimal, and generally limited to isolated neurons and astrocytes in the cerebral peduncles. GFP immunoreactivity (-ir) in thalamus was most prominent in medial geniculate nucleus, and otherwise limited to posterior nuclei of the dorsal and lateral margins. Labeling was also observed in neurons and astrocytes of the hippocampal formation and amygdaloid complex. In the hippocampal formation, GFP-ir was found in neuronal cell bodies of the rostral ventral portion, but was largely restricted to fiber-like staining in the molecular layer of dentate gyrus and stratum lacunosum-moleculare of the rostral dorsal region. GFP-ir was seen in neurons and astroglia throughout caudal cortex, whereas in rostral regions of neocortex it was limited to isolated neurons and non-neuronal cells. Labeling was also present in olfactory bulb. These results demonstrate that intrathecal delivery of AAV5 vector leads to transgene expression in discrete CNS regions throughout the rostro-caudal extent of the neuraxis. A caudal-to-rostral gradient of decreasing GFP-ir was present in choroid plexus and Purkinje cells, suggesting that spread of virus through cerebrospinal fluid plays a role in the resulting transduction pattern. Other factors contributing to the observed expression pattern likely include variations in cell-surface receptors and inter-parenchymal space.

Distinct developmental growth patterns account for the disproportionate expansion of the rostral and caudal isocortex in evolution.

In adulthood, the isocortex of several species is characterized by a gradient in neurons per unit of cortical surface area with fewer neurons per unit of cortical surface area in the rostral pole relative to the caudal pole. A gradient in neurogenesis timing predicts differences in neurons across the isocortex: neurons per unit of cortical surface area are fewer rostrally, where neurogenesis duration is short, and higher caudally where neurogenesis duration is longer. How species differences in neurogenesis duration impact cortical progenitor cells across its axis is not known. I estimated progenitor cells per unit of ventricular area across the rostro-caudal axis of the isocortex in cats (Felis catus) and in dogs (Canis familiaris) mostly before layers VI-II neurons are generated. I also estimated the ventricular length across the rostro-caudal axis at various stages of development in both species. These two species were chosen because neurogenesis duration in dogs is extended compared with cats. Caudally, cortical progenitors expand more tangentially and in numbers in dogs compared with cats. Rostrally, the cortical proliferative zone expands more tangentially in dogs compared with cats. However, the tangential expansion in the rostral cortical proliferative zone occurs without a concomitant increase in progenitor cell numbers. The tangential expansion of the ventricular surface in the rostral cortex is mediated by a reduction in cell density. These different developmental growth patterns account for the disproportionate expansion of the rostral (i.e., frontal cortex) and caudal cortex (e.g., primary visual cortex) when neurogenesis duration lengthens in evolution.

RNA expression profiling in brains of familial hemiplegic migraine type 1 knock-in mice

Various CACNA1A missense mutations cause familial hemiplegic migraine type 1 (FHM1), a rare monogenic subtype of migraine with aura. FHM1 mutation R192Q is associated with pure hemiplegic migraine, whereas the S218L mutation causes hemiplegic migraine, cerebellar ataxia, seizures, and mild head trauma-induced brain edema. Transgenic knock-in (KI) migraine mouse models were generated that carried either the FHM1 R192Q or the S218L mutation and were shown to exhibit increased CaV2.1 channel activity. Here we investigated their cerebellar and caudal cortical transcriptome. Caudal cortical and cerebellar RNA expression profiles from mutant and wild-type mice were studied using microarrays. Respective brain regions were selected based on their relevance to migraine aura and ataxia. Relevant expression changes were further investigated at RNA and protein level by quantitative polymerase chain reaction (qPCR) and/or immunohistochemistry, respectively. Expression differences in the cerebellum were most pronounced in S218L mice. Particularly, tyrosine hydroxylase, a marker of delayed cerebellar maturation, appeared strongly upregulated in S218L cerebella. In contrast, only minimal expression differences were observed in the caudal cortex of either mutant mice strain. Despite pronounced consequences of migraine gene mutations at the neurobiological level, changes in cortical RNA expression in FHM1 migraine mice compared to wild-type are modest. In contrast, pronounced RNA expression changes are seen in the cerebellum of S218L mice and may explain their cerebellar ataxia phenotype.

Thalamocortical projections of the anterodorsal thalamic nucleus in the rabbit

The anterior thalamic nuclei consist of the anterodorsal (AD), anteroventral, and anteromedial nuclei, each of which are highly differentiated and may contribute to different aspects of various cognitive and memory functions. In particular, the AD is unique in that it is implicated in learning at the earliest stage of discriminative avoidance conditioning in the rabbit. To better understand the functional roles played by the AD in memory and learning processes, we analyzed the organization of thalamocortical projections of the AD in the rabbit, using the anterograde tracer biotinylated dextran amine and the retrograde tracer cholera toxin subunit B. The data show that the AD provides strong projections to layers I and IV of area 30 and to layers I, III, IV, and VI of area 29 in the retrosplenial cortex, and to layers I and III-VI of the presubiculum. The projections to the retrosplenial cortex are organized such that the rostral and caudal AD, respectively, project to the caudal and rostral retrosplenial cortex. In contrast, the projections to the presubiculum are not organized topographically. Other minor projections were also observed in the parasubiculum and part of the medial entorhinal area. These results indicate that the AD provides strong projections to the retrosplenial cortex and presubiculum, suggesting that these projections constitute essential pathways to these cortical regions for transmitting mnemonic information, such as a novel conditioning stimulus during the initial stage of avoidance learning.

Effective mechanical properties of diaphyseal cortical bone in the canine femur

The effective elastic modulus, yield strength, yield strain, ultimate strength, ultimate strain, strain energy density at yield and strain energy density at ultimate failure of femoral diaphyseal cortical bone were investigated on canine femurs. Four femurs representative of the canine population were selected from four statistically-determined clusters based on increasing size and weight comprising the Toy poodle (5 kg), Poodle (12 kg), German shorthaired pointer (25 kg) and Doberman (50 kg). The zones of interest were the lateral, medial, cranial, and caudal quadrants of the mid-diaphysis. Effective mechanical properties were measured using quasi-static three-point bending tests on strips. The averages ± SD were 15.6 ± 2.6 GPa for effective elastic modulus, 174.3 ± 32.1 MPa for yield strength, 0.012 ± 0.003 for yield strain, 251.0 ± 49.1 MPa for ultimate strength, 0.021 ± 0.005 for ultimate strain, 10.7 ± 4.0J m(-3) × 10(5) for strain energy density at Yield and 33.0 ± 14.1 Jm(-3)× 10(5) for strain energy density at ultimate failure. Significant differences were found between dogs and the effective elastic modulus increased with breed weight and size (13.9 GPa for the Toy poodle to 17.2 GPa for the Doberman). The ultimate strength σ(u) and strain energy density at ultimate failure U(u) were significantly lower in the Toy poodle than in the Poodle and German shorthaired pointer indicating that the cortical bone material in the Toy poodle differed from that of the other dogs. Examination of the zones of interest revealed that the cranial quadrant showed the greatest stiffness, whereas strength was highest at the medial site. The caudal cortex was less stiff and strong than the cranial cortex.

Chemoarchitecture of Layer 4 Isocortex in the American Water Shrew (Sorex palustris)

We examined the chemoarchitecture of layer 4 isocortex and the number of myelinated nerve fibers of selected cranial nerves in the American water shrew (Sorex palustris). This study took advantage of the opportunity to examine juvenile brain tissue, which often reveals the most distinctive cortical modules related to different sensory representations. Flattened cortical sections were processed for the metabolic enzyme cytochrome oxidase, revealing a number of modules and septa. Subdivisions related to sensory representations were tentatively identified by performing microelectrode recordings in a single adult shrew in this study, combined with microelectrode recordings and anatomical findings from a previous investigation. Taken together, these results suggest that characteristic chemoarchitectonic borders in the shrew neocortex can be used to delineate and quantify cortical areas. The most obvious subdivisions in the water shrew include a relatively small primary visual cortex which responded to visual stimuli, a larger representation of vibrissae in the primary somatosensory cortex, and a prominent representation of oral structures apparent in the more rostral-lateral cortex. A presumptive auditory area was located in the far caudal cortex. These findings for the cortex are consistent with counts from optic, auditory and trigeminal nerves, suggesting that somatosensory inputs dominate the shrew’s senses whereas visual and auditory inputs play a small role in navigation and in finding prey. More generally, we find that shrews share unusual features of cortical organization with moles, supporting their close taxonomic relationship.

Receptor-like Protein-tyrosine Phosphatase α Enhances Cell Surface Expression of Neural Adhesion Molecule NB-3

Neural adhesion molecule NB-3 plays an important role in the apical dendrite development of layer V pyramidal neurons in the visual cortex, and receptor-like protein-tyrosine phosphatase α (PTPα) mediates NB-3 signaling in this process. Here we investigated the role of PTPα in regulating cell surface expression of NB-3. We found that cortical neurons from PTPα knock-out mice exhibited a lower level of NB-3 at the cell surface. When expressed in COS1 cells, NB-3 was enriched in the Golgi apparatus with a low level of cell surface expression. However, co-expression of PTPα increased the cell surface distribution of NB-3. Further analysis showed that PTPα facilitated Golgi exit of NB-3 and stabilized NB-3 protein at the cell surface by preventing its release from the plasma membrane. The extracellular region of PTPα but not its catalytic activity is necessary for its effect on NB-3 expression. Thus, the PTPα-mediated increase of NB-3 level at the cell surface represents a novel function of PTPα in NB-3 signaling in neural development.

Fgfr3 regulates development of the caudal telencephalon

The fibroblast growth factor receptor 3 (Fgfr3) is expressed in a rostral(low) to caudal(high) gradient in the developing cerebral cortex. Therefore, we hypothesized that Fgfr3 contributes to the correct morphology and connectivity of the caudal cortex. Overall, the forebrain structures appeared normal in Fgfr3(-/-) mice. However, cortical and hippocampal volumes were reduced by 26.7% and 16.3%, respectively. Hypoplasia was particularly evident in the caudo-ventral region of the telencephalon where proliferation was mildly decreased at embryonic day 18.5. Dysplasia of GABAergic neurons in the amygdala and piriform cortex was seen following GAD67 immunohistochemistry. Dye-tracing studies and diffusion magnetic resonance imaging and tractography detected a subtle thalamocortical tract deficit, and significant decreases in the stria terminalis and lateral arms of the anterior commissure. These results indicate the subtle role of Fgfr3 in formation of caudal regions of the telencephalon affecting some brain projections.

Aβ Accelerates the Spatiotemporal Progression of Tau Pathology and Augments Tau Amyloidosis in an Alzheimer Mouse Model

Senile plaques formed by β-amyloid peptides (Aβ) and neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau, a microtubule-associated protein, are the hallmark lesions of Alzheimer's disease (AD) in addition to loss of neurons. While several transgenic (Tg) mouse models have recapitulated aspects of AD-like Aβ and tau pathologies, a spatiotemporal mapping paradigm for progressive NFT accumulation is urgently needed to stage disease progression in AD mouse models. Braak and co-workers developed an effective and widely used NFT staging paradigm for human AD brains. The creation of a Braak-like spatiotemporal staging scheme for tau pathology in mouse models would facilitate mechanistic studies of AD-like tau pathology. Such a scheme would also enhance the reproducibility of preclinical AD therapeutic studies. Thus, we developed a novel murine model of Aβ and tau pathologies and devised a spatiotemporal scheme to stage the emergence and accumulation of NFTs with advancing age. Notably, the development of NFTs followed a spatiotemporal Braak-like pattern similar to that observed in authentic AD. More significantly, the presence of Aβ accelerated NFT formation and enhanced tau amyloidosis; however, tau pathology did not have the same effect on Aβ pathology. This novel NFT staging scheme provides new insights into the mechanisms of tau pathobiology, and we speculate that this scheme will prove useful for other basic and translational studies of AD mouse models.

Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex

Areas and layers of the cerebral cortex are specified by genetic programs that are initiated in progenitor cells and then, implemented in postmitotic neurons. Here, we report that Tbr1, a transcription factor expressed in postmitotic projection neurons, exerts positive and negative control over both regional (areal) and laminar identity. Tbr1 null mice exhibited profound defects of frontal cortex and layer 6 differentiation, as indicated by down-regulation of gene-expression markers such as Bcl6 and Cdh9. Conversely, genes that implement caudal cortex and layer 5 identity, such as Bhlhb5 and Fezf2, were up-regulated in Tbr1 mutants. Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2, a frontal cortex gene implicated in autism. Tbr1 regulates laminar identity in part by downstream activation or maintenance of Sox5, an important transcription factor controlling neuronal migration and corticofugal axon projections. Similar to Sox5 mutants, Tbr1 mutants exhibit ectopic axon projections to the hypothalamus and cerebral peduncle. Together, our findings show that Tbr1 coordinately regulates regional and laminar identity of postmitotic cortical neurons.

Effect of Cranial Tibial Closing Wedge Angle on Tibial Subluxation: An Ex Vivo Study

To evaluate the effect of cranial tibial wedge osteotomy (CTWO) angle on cranial tibial subluxation (CTS) and postoperative tibial plateau angle (TPA). Ex vivo biomechanical study. Canine pelvic limbs (n=6). TPA determined from a lateral radiographic projection. CTS under 30% body weight load was measured from radiographs in the intact limb and after transection of the cranial cruciate ligament. A CTWO equal to TPA+10 degrees was performed at the distal extent of the tibial crest, and was stabilized with a custom designed hinge plate and external skeletal fixator. TPA and CTS in the loaded limb was determined from radiographs at 4 CTWO angles: TPA-5 degrees, TPA, TPA+5 degrees, and TPA+7.5 degrees. Comparison of CTS between the intact limb and the 4 CTWO angle groups was performed using 1-way repeated-measures ANOVA and a Dunnett multiple comparison test (significance at P<.05). CTS was significantly greater than that of the intact limb in the TPA-5 degrees and TPA groups. CTS was not significantly different from the intact limb in the TPA+5 degrees or TPA+7.5 degrees groups with corresponding TPAs of 5.9 degrees and 3.8 degrees, respectively. Using this model, CTS was neutralized at a TPA of approximately 4-6 degrees with a CTWO angle between TPA+5 degrees and TPA+7.5 degrees. A CTWO angle between TPA+5 degrees and TPA+7.5 degrees is necessary to neutralize CTS and achieve a postoperative TPA of 4-6 degrees if the CTWO is performed at the distal extent of the tibial crest and the caudal cortices are aligned.

Functional MRI study about Chinese character radicals identification in school children

Objective To explore the specific brain regions involved in Chinese character radicals visualspatial processing,as well as to explore the relationship between visual-spatial identification and Chinese characters radicals identification.To provide an evidence for understanding the underlying neural mechanism of developmental dyslexic.Methods Twelve healthy Chinese fourth and fifth grade children(7 boys and 2 girls,aged from 10 to 11 years old)were chosen from a primary school in Guangzhou.The children were native Chinese speakers and right handed.The subjects participated in two fMRI experiments on a 3.0 T Siemens MR scanner.Two separate block-designed cognitive tasks were devised,one was figure directions judgement task and the other was Chinese characters radical identification task.A single-shot GE-EPI scan sequence were used for fMRI scans.The BOLD fMRI data were collected and were preprocessed and analyzed in SPM2.Results The subjects had longer reaction time during the two experiments tasks than in control states((879±127)ms vs(805±124)ms,P=0.029;(917±144)ms vs(750±101)ms,P＜0.01),and had same response accuracy in both tasks and control states((96±5)% vs(95±8)%,P=0.515;(89±10)% vs(96±6)%,P=0.130).In figure direction judgement experiment,activations were found in bilateral occipital,right superior parietal,right precuneus and right middle frontal cortices.However,different and more extensive regions including left superior parietal,left precuneus,left hippocampus,right thalamus,right caudate cortices and bilateral occipital cortices were involved in identifying the radicals of Chinese characters.Conclusion Right hemisphere was dominant in judging the figure direction,and left hemisphere is dominant in identifying radicals of Chinese characters.These fMRI results show light on underlying partial similar neurophysiological mechanism between judging figure directions and identifying Chinese character radicals.The visual-spatial ability may be essential for Chinese character radical identification. Key words: fMRI; Children; Reading; Chinese

Digital Radiographic Analysis of Optical Density of the Distal Segment of the Trochlear Notch of the Ulna in Labrador Retrievers with Fragmented Coronoid Process

The aim of the study was to find whether there is a difference in the optical density of the subtrochlear region of incisura trochlearis and in the region of processus coronoideus medialis ulnae in elbow joints with fragmented processus coronoideus and in healthy elbow joints of the Labrador retriever breed. We evaluated digital radiographs of elbows (n = 26) with arthroscopically or arthrotomically proven FCP and digital radiographs of healthy elbows (n = 28). A template was made on radiographs in the JiveX program (Visus Technology Transfer) demarcating individual regions of interest (ROI) in which median optical density was measured. For normalisation of median optical density data of individual ROI, median optical density of the caudal ulnar cortex was used. Elbow joints with fragmented processus coronoideus had a lower mean median optical density in the distal part of incisura trochlearis compared to healthy elbow joints. The lowest median optical densities were found in the region of processus coronoideus medialis and in the distal part of the trochlear notch of the ulna in the region of processus coronoideus lateralis. The biggest difference in median optical densities between elbows with FCP and healthy elbows was found in regions distant from the articular surface. In evaluation of the opacity of the trochlear notch of the ulna it is appropriate to assess the whole region of the proximal ulnar metaphysis from the articular surface to the caudal ulnar cortex.

12-P017 Fgfr3 regulates development of the caudal cerebral cortex

12-P017 Fgfr3 regulates development of the caudal cerebral cortex

Fgf10 Regulates Transition Period of Cortical Stem Cell Differentiation to Radial Glia Controlling Generation of Neurons and Basal Progenitors

Radial glia (RG), the progenitors of cortical neurons and basal progenitors (BPs), differentiate from neuroepithelial cells (NCs) with stem cell properties. We show that the morphogen Fgf10 is transiently expressed by NCs coincident with the transition period of NC differentiation into RG. Targeted deletion of Fgf10 delays RG differentiation, whereas overexpression has opposing effects. Delayed RG differentiation in Fgf10 mutants occurs selectively in rostral cortex, paralleled by an extended period of symmetric NC divisions increasing progenitor number, coupled with delayed and initially diminished production of neurons and BPs. RG eventually differentiate in excess number and overproduce neurons and BPs rostrally resulting in tangential expansion of frontal areas and increased laminar thickness. Thus, transient Fgf10 expression regulates timely differentiation of RG, and through this function, determines both length of the early progenitor expansion phase and onset of neurogenesis and ultimately the number of progenitors and neurons fated to specific cortical areas.

Self-Organized Formation of Polarized Cortical Tissues from ESCs and Its Active Manipulation by Extrinsic Signals

Here, we demonstrate self-organized formation of apico-basally polarized cortical tissues from ESCs using an efficient three-dimensional aggregation culture (SFEBq culture). The generated cortical neurons are functional, transplantable, and capable of forming proper long-range connections in vivo and in vitro. The regional identity of the generated pallial tissues can be selectively controlled (into olfactory bulb, rostral and caudal cortices, hem, and choroid plexus) by secreted patterning factors such as Fgf, Wnt, and BMP. In addition, the in vivo-mimicking birth order of distinct cortical neurons permits the selective generation of particular layer-specific neurons by timed induction of cell-cycle exit. Importantly, cortical tissues generated from mouse and human ESCs form a self-organized structure that includes four distinct zones (ventricular, early and late cortical-plate, and Cajal-Retzius cell zones) along the apico-basal direction. Thus, spatial and temporal aspects of early corticogenesis are recapitulated and can be manipulated in this ESC culture.

ZicDeficiency in the Cortical Marginal Zone and Meninges Results in Cortical Lamination Defects Resembling Those in Type II Lissencephaly

The formation of the highly organized cortical structure depends on the production and correct placement of the appropriate number and types of neurons. The Zic family of zinc-finger transcription factors plays essential roles in regulating the proliferation and differentiation of neuronal progenitors in the medial forebrain and the cerebellum. Examination of the expression of Zic genes demonstrated that Zic1, Zic2, and Zic3 were expressed by the progenitor cells in the septum and cortical hem, the sites of generation of the Cajal-Retzius (CR) cells. Immunohistochemical studies have revealed that Zic proteins were abundantly expressed in the meningeal cells and that the majority of the CR cells distributed in the medial and dorsal cortex also expressed Zic proteins in the mid-late embryonic and postnatal cortical marginal zones. During embryonic cortical development, Zic1/Zic3 double-mutant and hypomorphic Zic2 mutant mice showed a reduction in the number of CR cells in the rostral cortex, whereas the cell number remained unaffected in the caudal cortex. These mutants also showed mislocalization of the CR cells and cortical lamination defects, resembling the changes noted in type II (cobblestone) lissencephaly, throughout the brain. In the Zic1/3 mutant, reduced proliferation of the meningeal cells was observed before the thinner and disrupted organization of the pial basement membrane (BM) with reduced expression of the BM components and the meningeal cell-derived secretory factor. These defects correlated with the changes in the end feet morphology of the radial glial cells. These findings indicate that the Zic genes play critical roles in cortical development through regulating the proliferation of meningeal cells and the pial BM assembly.

GFAP promoter elements required for region‐specific and astrocyte‐specific expression

Glial fibrillary acidic protein (GFAP) is the major intermediate filament protein in astrocytes, one of the most abundant cell types in the vertebrate central nervous system (CNS). Transcriptional regulation of GFAP is of interest because of its astrocyte-specificity and its upregulation during development and CNS injury. A 2.2 kb human GFAP promoter, gfa2, has been found to express in astrocytes throughout the CNS. In contrast, we recently found that the 448 bp gfa28 promoter expresses in only restricted CNS regions, and is active in neurons as well as astrocytes. In the present study we have used transgenic mice to investigate which DNA regions deleted from gfa2 in the formation of gfa28 are responsible for these differences. We have found that a 55 bp segment spanning bp -1488 to -1434 with respect to the RNA start site contains region-specific elements and that a 45 bp sequence spanning bp -1443 to -1399 is required for silencing expression in neurons. These data also further confirm the heterogeneity of astrocytes and neurons in the activation and repression of the GFAP gene, respectively. These studies also generated a novel 681 bp GFAP promoter, gfaABC(1)D, that has essentially the same expression pattern as the 2210 bp gfa2 promoter, and about twofold greater activity, recommending it for gene targeting applications in which size matters. In addition, a 681 bp gfaABC(1)(mC(1.1))D variant was generated that could limit expression of transgenes to astrocytes in the dorsal and caudal cortex, hippocampus and caudal vermis of the cerebellum.

Neural recognition molecules CHL1 and NB-3 regulate apical dendrite orientation in the neocortex via PTPα

Apical dendrites of pyramidal neurons in the neocortex have a stereotypic orientation that is important for neuronal function. Neural recognition molecule Close Homolog of L1 (CHL1) has been shown to regulate oriented growth of apical dendrites in the mouse caudal cortex. Here we show that CHL1 directly associates with NB-3, a member of the F3/contactin family of neural recognition molecules, and enhances its cell surface expression. Similar to CHL1, NB-3 exhibits high-caudal to low-rostral expression in the deep layer neurons of the neocortex. NB-3-deficient mice show abnormal apical dendrite projections of deep layer pyramidal neurons in the visual cortex. Both CHL1 and NB-3 interact with protein tyrosine phosphatase alpha (PTPalpha) and regulate its activity. Moreover, deep layer pyramidal neurons of PTPalpha-deficient mice develop misoriented, even inverted, apical dendrites. We propose a signaling complex in which PTPalpha mediates CHL1 and NB-3-regulated apical dendrite projection in the developing caudal cortex.

Novel genes differentially expressed in cortical regions during late neurogenesis

Differential gene expression across the embryonic cerebral cortex is assumed to play a role in the subdivision of the cortex into distinct areas with specific morphology, physiology and function. In a search for genes that may be involved in the cortical regionalization during late neurogenesis in mouse, we performed an extensive in-situ expression analysis at embryonic day (E)16 and E18. The examined candidate genes were selected beforehand by a microarray screen by virtue of their preferential expression in the anlagen of the motor, somatosensory, visual and cingulate cortices or hippocampus. We present new information about graded or regionally enriched expression of 25 genes (nine of which are novel genes) across the mouse embryonic cortex, in progenitor cells as well as in the cortical plate. The established differential expression of most of these genes is persistent at both stages studied, suggesting that their expression is regulated by an intrinsic programme. For some of the genes, the concept of intrinsic regulation is further substantiated by the high similarity of the reported expression patterns at E16 and E18 and published data from earlier stages. Few genes with robust expression in the E16 caudal cortex showed a more restricted pattern at E18, possibly because of their response to extrinsic cues. In addition, several genes appeared to be suitable novel markers for amygdalar and diencephalic nuclei. Taken together, our findings reveal novel molecular partitions of the late mouse cortex that are in accordance with the model of a leading role of intrinsic mechanisms in cortical arealization.