Postmitotic neurons migrate tangentially in the cortical ventricular zone

Development ◽  
1997 ◽  
Vol 124 (5) ◽  
pp. 997-1005 ◽  
Author(s):  
N.A. O'Rourke ◽  
A. Chenn ◽  
S.K. McConnell
Keyword(s):  
Ventricular Zone ◽  
Cell Movement ◽  
Specific Marker ◽  
Cortical Cells ◽  
Neuronal Progenitor ◽  
Proliferative Zone ◽  
Postmitotic Neurons ◽  
Subventricular Zones ◽  
Migratory Patterns ◽  
Intact Cortex

Patterns of cell movement play a key role in the establishment of the brain's functional architecture during development. The migration of neuronal progenitor cells has been hypothesized to disperse clonally related cells among different areas of the developing cerebral cortex. To test this model, we explored the migratory patterns of cells in the proliferative zone of the intact cortex of the ferret. After focal injections of DiI, labeled cells migrated in all directions and over long distances within the ventricular and subventricular zones. These cells expressed the neuron-specific marker TuJ1 and did not incorporate BrdU after cumulative labeling. Our results reveal an extensive tangential dispersion of cortical cells mediated predominantly or exclusively by the non-radial migration of postmitotic neurons.

PAX2 is expressed in multiple spinal cord interneurons, including a population of EN1+ interneurons that require PAX6 for their development

Development ◽  
1997 ◽  
Vol 124 (22) ◽  
pp. 4493-4503 ◽  
Author(s):  
J.D. Burrill ◽  
L. Moran ◽  
M.D. Goulding ◽  
H. Saueressig
Keyword(s):  
Spinal Cord ◽  
Transcription Factors ◽  
Ventricular Zone ◽  
Cell Types ◽  
Cell Identity ◽  
Patterning Genes ◽  
Postmitotic Neurons ◽  
Pax Family ◽  
Early Activity

Members of the PAX family of transcription factors are candidates for controlling cell identity in the spinal cord. We have morphologically analyzed cells that express one of these transcription factors, PAX2, demonstrating multiple interneuron cell types express PAX2. Two ventral populations of PAX2-expressing interneurons in the spinal cord are marked by coexpression of the transcription factors, EN1 and EVX1. Interestingly, the expression domains of PAX2, EN1 and EVX1 in postmitotic neurons correlate closely with those of Pax6 and Pax7 in the ventricular zone, implicating these patterning genes in the regulation of PAX2, EN1 and EVX1. We show that one of these patterning genes, Pax6, is required for the correct specification of ventral PAX2+ interneurons that coexpress EN1. These results demonstrate that the early activity of patterning genes in the ventricular zone determines interneuron identity in the spinal cord.

scholarly journals Interplay of SOX and POU Factors in Regulation of the Nestin Gene in Neural Primordial Cells

2004 ◽  
Vol 24 (20) ◽  
pp. 8834-8846 ◽  
Author(s):  
Shinya Tanaka ◽  
Yusuke Kamachi ◽  
Aki Tanouchi ◽  
Hiroshi Hamada ◽  
Naihe Jing ◽  
...  
Keyword(s):  
Binding Sites ◽  
Ventricular Zone ◽  
Class Iii ◽  
High Level Expression ◽  
Enhancer Activity ◽  
Mouse Spinal Cord ◽  
Regulatory Link ◽  
Subventricular Zones ◽  
High Level ◽  
Expression Evidence

ABSTRACT Intermediate-filament Nestin and group B1 SOX transcription factors (SOX1/2/3) are often employed as markers for neural primordium, suggesting their regulatory link. We have identified adjacent and essential SOX and POU factor binding sites in the Nestin neural enhancer. The 30-bp sequence of the enhancer including these sites (Nes30) showed a nervous system-specific and SOX-POU-dependent enhancer activity in multimeric forms in transfection assays and was utilized in assessing the specificity of the synergism; combinations of either group B1 or group C SOX (SOX11) with class III POU proved effective. In embryonic day 13.5 mouse spinal cord, Nestin was expressed in the cells with nuclei in the ventricular and subventricular zones. SOX1/2/3 expression was confined to the nuclei of the ventricular zone; SOX11 localized to the nuclei of both subventricular (high-level expression) and intermediate (low-level expression) zones. Class III POU (Brn2) was expressed at high levels, localizing to the nucleus in the ventricular and subventricular zones; moderate expression was observed in the intermediate zone, distributed in the cytoplasm. These data support the model that synergic interactions between group B1/C SOX and class III POU within the nucleus determine Nestin expression. Evidence also suggests that such interactions are involved in the regulation of neural primordial cells.

scholarly journals Maternal Leukemia Inhibitory Factor (LIF) Promotes Fetal Neurogenesis via a LIF-ACTH-LIF Signaling Relay Pathway

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1853-1862 ◽  
Author(s):  
Eriko Simamura ◽  
Hiroki Shimada ◽  
Nobuaki Higashi ◽  
Maimi Uchishiba ◽  
Hiroki Otani ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Leukemia Inhibitory Factor ◽  
Ventricular Zone ◽  
Fetal Brain ◽  
Inhibitory Factor ◽  
Neuronal Progenitor ◽  
Nucleated Red Blood Cells ◽  
Show Evidence

Leukemia inhibitory factor (LIF) promotes the proliferation of neuronal progenitor cells in the cerebrum. However, it remains unclear how fetal LIF level is regulated. Here we show evidence that maternal LIF signals drive fetal LIF levels via the placenta, thereby promoting neurogenesis in the fetal brain in rats. Chronological changes showed that LIF concentration in fetal sera (FS) and fetal cerebrospinal fluid peaked at gestational day (GD) 15.5, after the peak of maternal LIF at GD14.5. LIF injection into rat dams at GD15.5 increased the level of ACTH in FS and subsequently increased LIF levels in FS and fetal cerebrospinal fluid. The elevation of fetal LIF after LIF injection into dams was inhibited by in utero injection of anti-ACTH antibody into fetuses. Cultured syncytiotrophoblasts, which express the LIF receptor and glycoprotein 130, were induced to secrete ACTH and up-regulate Pomc expression by the addition of LIF. Nucleated red blood cells from fetuses at GD15.5, but not GD13.5 or GD17.5, displayed LIF secretion in response to ACTH. Moreover, injection of LIF into dams at GD13.5 or GD17.5 did not result in elevation of ACTH or LIF in fetuses. The labeling index of 5-bromo-2′-deoxyuridine-positive cells in the ventricular zone of the cerebral neocortex increased 24 h after injection of LIF into dams at GD15.5 but not GD13.5 or GD17.5. These results suggest that in rats maternal LIF induces ACTH from the placenta, which in turn induces fetal nucleated red blood cells to secrete LIF that finally increases neurogenesis in fetuses around GD15.

Tangential migration of neurons in the developing cerebral cortex

Development ◽  
1995 ◽  
Vol 121 (7) ◽  
pp. 2165-2176 ◽  
Author(s):  
N.A. O'Rourke ◽  
D.P. Sullivan ◽  
C.E. Kaznowski ◽  
A.A. Jacobs ◽  
S.K. McConnell
Keyword(s):  
Cerebral Cortex ◽  
Neuronal Migration ◽  
Ventricular Zone ◽  
Brain Slices ◽  
Cortical Plate ◽  
Tangential Migration ◽  
Cortical Regions ◽  
Intact Cortex ◽  
Migrating Cells

The mammalian cerebral cortex is divided into functionally distinct areas. Although radial patterns of neuronal migration have been thought to be essential for patterning these areas, direct observation of migrating cells in cortical brain slices has revealed that cells follow both radial and nonradial pathways as they travel from their sites of origin in the ventricular zone out to their destinations in the cortical plate (O'Rourke, N.A., Dailey, M.E., Smith, S.J. and McConnell, S.K. (1992) Science 258, 299–302). These findings suggested that neurons may not be confined to radial migratory pathways in vivo. Here, we have examined the patterns of neuronal migration in the intact cortex. Analysis of the orientations of [3H]thymidine-labeled migrating cells suggests that nonradial migration is equally common in brain slices and the intact cortex and that it increases during neurogenesis. Additionally, cells appear to follow nonradial trajectories at all levels of the developing cerebral wall, suggesting that tangential migration may be more prevalent than previously suspected from the imaging studies. Immunostaining with neuron-specific antibodies revealed that many tangentially migrating cells are young neurons. These results suggest that tangential migration in the intact cortex plays a pivotal role in the tangential dispersion of clonally related cells revealed by retroviral lineage studies (Walsh, C. and Cepko, C. L. (1992) Science 255, 434–440). Finally, we examined possible substrata for nonradial migration in dorsal cortical regions where the majority of glia extend radially. Using confocal and electron microscopy, we found that nonradially oriented cells run perpendicular to glial processes and make glancing contacts with them along their leading processes. Thus, if nonradial cells utilize glia as a migratory substratum they must glide across one glial fiber to another. Examination of the relationships between migratory cells and axons revealed axonal contacts with both radial and nonradial cells. These results suggest that nonradial cells use strategies and substrata for migration that differ from those employed by radial cells.

Pax6 is required to regulate the cell cycle and the rate of progression from symmetrical to asymmetrical division in mammalian cortical progenitors

Development ◽  
2002 ◽  
Vol 129 (2) ◽  
pp. 455-466 ◽  
Author(s):  
Guillermo Estivill-Torrus ◽  
Helen Pearson ◽  
Veronica van Heyningen ◽  
David J. Price ◽  
Penny Rashbass
Keyword(s):  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Cycle Duration ◽  
Differentiation Markers ◽  
Cortical Cells ◽  
Proliferative Zone ◽  
Rate Of Progression ◽  
Asymmetrical Division ◽  
Asymmetrical Divisions

In the proliferative zone of the developing cerebral cortex, multipotential progenitors predominate early in development and divide to increase the progenitor pool. As corticogenesis progresses, proportionately fewer progenitors are produced and, instead, cell divisions yield higher numbers of postmitotic neurones or glial cells. As the switch from the generation of progenitors to that of differentiated cells occurs, the orientation of cell division alters from predominantly symmetrical to predominantly asymmetrical. It has been hypothesised that symmetrical divisions expand the progenitor pool, whereas asymmetrical divisions generate postmitotic cells, although this remains to be proved. The molecular mechanisms regulating these processes are poorly understood. The transcription factor Pax6 is highly expressed in the cortical proliferative zone and there are morphological defects in the Pax6Sey/Sey (Pax6 null) cortex, but little is known about the principal cellular functions of Pax6 in this region. We have analysed the cell-cycle kinetics, the progenitor cleavage orientation and the onset of expression of differentiation markers in Pax6Sey/Sey cortical cells in vivo and in vitro. We showed that, early in corticogenesis at embryonic day (E) 12.5, the absence of Pax6 accelerated cortical development in vivo, shortening the cell cycle and the time taken for the onset of expression of neural-specific markers. This also occurred in dissociated culture of isolated cortical cells, indicating that the changes were intrinsic to the cortical cells. From E12.5 to E15.5, proportions of asymmetrical divisions increased more rapidly in mutant than in wild-type embryos. By E15.5, interkinetic nuclear migration during the cell cycle was disrupted and the length of the cell cycle was significantly longer than normal in the Pax6Sey/Sey cortex, with a lengthening of S phase. Together, these results show that Pax6 is required in developing cortical progenitors to control the cell-cycle duration, the rate of progression from symmetrical to asymmetrical division and the onset of expression of neural-specific markers.

scholarly journals Local and thalamic origins of ongoing and sensory evoked cortical correlations

2016 ◽  
Author(s):  
Katayun Cohen-Kashi Malina ◽  
Boaz Mohar ◽  
Akiva N. Rappaport ◽  
Miao Liu
Keyword(s):  
Barrel Cortex ◽  
Field Potential ◽  
Sensory Response ◽  
Cortical Cells ◽  
Synaptic Inputs ◽  
Correlated Activity ◽  
Layer 4 ◽  
Lower Variability ◽  
Intact Cortex ◽  
Sensory Evoked

Thalamic inputs of layer 4 (L4) cells in sensory cortices are outnumbered by local connections. Thus, it was suggested that robust sensory response in L4 emerges due to synchronized thalamic activity. In order to investigate the role of both inputs in generation of cortical synchronization, we isolated the thalamic excitatory inputs of cortical cells by optogenetically silencing cortical firing. In anesthetized mice, we measured the correlation between isolated thalamic synaptic inputs of simultaneously patched nearby L4 cells of the barrel cortex. In contrast to correlated activity of excitatory synaptic inputs in the intact cortex, isolated thalamic inputs exhibit lower variability and asynchronous spontaneous and sensory evoked inputs. These results were further supported in awake mice when we recorded the excitatory inputs of individual cortical cells simultaneously with the local field potential (LFP) in a nearby site. Our results therefore indicate that cortical synchronization emerges by intracortical coupling.

scholarly journals Bves and NDRG4 regulate directional epicardial cell migration through autocrine extracellular matrix deposition

2013 ◽  
Vol 24 (22) ◽  
pp. 3496-3510 ◽  
Author(s):  
Emily C. Benesh ◽  
Paul M. Miller ◽  
Elise R. Pfaltzgraff ◽  
Nathan E. Grega-Larson ◽  
Hillary A. Hager ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Heart Development ◽  
Cell Movement ◽  
Directed Movement ◽  
Protein Protein Interaction ◽  
Matrix Deposition ◽  
Directional Movement ◽  
Epicardial Cell ◽  
Migratory Patterns ◽  
Gene 4

Directional cell movement is universally required for tissue morphogenesis. Although it is known that cell/matrix interactions are essential for directional movement in heart development, the mechanisms governing these interactions require elucidation. Here we demonstrate that a novel protein/protein interaction between blood vessel epicardial substance (Bves) and N-myc downstream regulated gene 4 (NDRG4) is critical for regulation of epicardial cell directional movement, as disruption of this interaction randomizes migratory patterns. Our studies show that Bves/NDRG4 interaction is required for trafficking of internalized fibronectin through the “autocrine extracellular matrix (ECM) deposition” fibronectin recycling pathway. Of importance, we demonstrate that Bves/NDRG4-mediated fibronectin recycling is indeed essential for epicardial cell directional movement, thus linking these two cell processes. Finally, total internal reflectance fluorescence microscopy shows that Bves/NDRG4 interaction is required for fusion of recycling endosomes with the basal cell surface, providing a molecular mechanism of motility substrate delivery that regulates cell directional movement. This is the first evidence of a molecular function for Bves and NDRG4 proteins within broader subcellular trafficking paradigms. These data identify novel regulators of a critical vesicle-docking step required for autocrine ECM deposition and explain how Bves facilitates cell-microenvironment interactions in the regulation of epicardial cell–directed movement.

scholarly journals The Early Nodulin Gene MtN6 Is a Novel Marker for Events Preceding Infection of Medicago truncatula Roots by Sinorhizobium meliloti

1999 ◽  
Vol 12 (6) ◽  
pp. 544-555 ◽  
Author(s):  
R. Mathis ◽  
C. Grosjean ◽  
F. de Billy ◽  
T. Huguet ◽  
P. Gamas
Keyword(s):  
Medicago Truncatula ◽  
Sinorhizobium Meliloti ◽  
Root Nodules ◽  
Cdna Clones ◽  
Specific Marker ◽  
Nod Factors ◽  
Cortical Cells ◽  
Infection Threads ◽  
Early Nodulin ◽  
Cell Layers

MtN6 belongs to a series of cDNA clones representing Medicago truncatula genes transcriptionally activated during nodulation by Sinorhizobium meliloti (P. Gamas, F. de Carvalho Niebel, N. Lescure, and J. V. Cullimore, Mol. Plant-Microbe Interact. 9:233–242, 1996). We show here by in situ hybridization that MtN6 transcripts specifically accumulate first at very localized regions in the outer root cell layers, corresponding to outer cortical cells containing preinfection threads. At later stages, MtN6 expression is observed ahead of growing infection threads, including in the infection zone of mature root nodules. Interestingly, regulation of MtN6 is clearly distinct from that of other early nodulins expressed in the same region of the nodule, in terms of response to bacterial symbiotic mutants and to purified Nod factors. We thus suggest that MtN6 represents the first specific marker of a pathway involved in preparation to infection, which is at least partly controlled by Nod factors. Finally, we discuss the intriguing sequence homology shown by MtN6 to a protein from Emericella (Aspergillus) nidulans, FluG, that plays a key role in controlling the organogenesis of conidiophores (B. N. Lee and T. H. Adams, Genes Dev. 8:641–651, 1994).

Immunohistochemical Localization of Erythropoietin and Its Receptor in the Developing Human Brain

1999 ◽  
Vol 2 (2) ◽  
pp. 148-158 ◽  
Author(s):  
Sandra E. Juul ◽  
Anthony T. Yachnis ◽  
Amyn M. Rojiani ◽  
Robert D. Christensen
Keyword(s):  
Human Brain ◽  
Ventricular Zone ◽  
Immunohistochemical Localization ◽  
Surgical Removal ◽  
Term Infants ◽  
Neuron Populations ◽  
Specific Distribution ◽  
Germinal Zone ◽  
Subventricular Zones ◽  
Human Brains

We have previously shown erythropoietin (Epo) and its receptor (Epo-R) to be present in the fetal human central nervous system (CNS), and Epo to be present in the spinal fluid of normal preterm and term infants. To investigate the cellular specificities and developmental patterns of expression of these polypeptides in the human brain—areas that have not been well researched—we designed the following study. Human brains ranging in maturity from 5 weeks post-conception to adult were preserved at the time of elective abortion, surgical removal (tubal pregnancy, or removal for temporal lobe epilepsy), or autopsy. Immunohistochemistry was used to localize Epo and Epo-R reactivity in brains of different stages of development. Astrocytes, neurons, and microglia were identified in sequential tissue sections by specific antibodies. At 5 to 6 weeks post-conception, both Epo and Epo-R localized to cells in the periventricular germinal zone. At 10 weeks post-conception, Epo immunoreactivity was present throughout the cortical wall, with the most intense immunoreactivity present in the ventricular and subventricular zones. Epo-R, in contrast, was localized primarily to the subventricular zone, with little staining evident in the ventricular zone. In late fetal brains, Epo-R reactivity was most prominent in astrocytic cells, although modest reactivity was observed in certain neuron populations. In contrast, Epo staining localized primarily to neurons in fetal brains, although a subpopulation of astrocytes was also immunoreactive. In postnatal brains, both astrocyte and neuron populations were immunoreactive with antibodies to Epo-R and Epo. From these results it is clear that Epo and its receptor are present in the developing human brain as early as 5 weeks post-conception, and each protein shows a specific distribution that changes with development. We speculate that Epo is important in neurodevelopment, and that it also plays a role in brain homeostasis later in life, functioning in an autocrine or paracrine manner.

Determination of the migratory capacity of embryonic cortical cells lacking the transcription factor Pax-6

Development ◽  
1997 ◽  
Vol 124 (24) ◽  
pp. 5087-5096 ◽  
Author(s):  
D. Caric ◽  
D. Gooday ◽  
R.E. Hill ◽  
S.K. McConnell ◽  
D.J. Price
Keyword(s):  
Transcription Factor ◽  
Ventricular Zone ◽  
Wild Type Mouse ◽  
Wild Type ◽  
Cortical Cells ◽  
Developmental Potential ◽  
Neuronal Precursors ◽  
Cortical Precursors

The cerebral cortex forms by the orderly migration and subsequent differentiation of neuronal precursors generated in the proliferative ventricular zone. We studied the role of the transcription factor Pax-6, which is expressed in the ventricular zone, in cortical development. Embryos homozygous for a mutation of Pax-6 (Small eye; Sey) had abnormalities suggesting defective migration of late-born cortical precursors. When late-born Sey/Sey precursors were transplanted into wild-type embryonic rat cortex, they showed similar integrative, migrational and differentiative abilities to those of transplanted wild-type mouse precursors. These results suggest that postmitotic cortical cells do not need Pax-6 to acquire the capacity to migrate and differentiate, but that Pax-6 generates a cortical environment that permits later-born precursors to express their full developmental potential.

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