Spatiotemporal selectivity of response to Notch1 signals in mammalian forebrain precursors

Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 689-702 ◽  
Author(s):  
C.B. Chambers ◽  
Y. Peng ◽  
H. Nguyen ◽  
N. Gaiano ◽  
G. Fishell ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Cell Fate ◽  
Subventricular Zone ◽  
Cellular Proliferation ◽  
Precursor Cells ◽  
Temporal Cues ◽  
Short And Long Term ◽  
Cortical Regions ◽  
Anterior Subventricular Zone

The olfactory bulb, neocortex and archicortex arise from a common pool of progenitors in the dorsal telencephalon. We studied the consequences of supplying excess Notch1 signal in vivo on the cellular and regional destinies of telencephalic precursors using bicistronic replication defective retroviruses. After ventricular injections mid-neurogenesis (E14.5), activated Notch1 retrovirus markedly inhibited the generation of neurons from telencephalic precursors, delayed the emergence of cells from the subventricular zone (SVZ), and produced an augmentation of glial progeny in the neo- and archicortex. However, activated Notch1 had a distinct effect on the progenitors of the olfactory bulb, markedly reducing the numbers of cells of any type that migrated there. To elucidate the mechanism of the cell fate changes elicited by Notch1 signals in the cortical regions, short- and long-term cultures of E14.5 telencephalic progenitors were examined. These studies reveal that activated Notch1 elicits a cessation of proliferation that coincides with an inhibition of the generation of neurons. Later, during gliogenesis, activated Notch1 triggers a rapid cellular proliferation with a significant increase in the generation of cells expressing GFAP. To examine the generation of cells destined for the olfactory bulb, we used stereotaxic injections into the early postnatal anterior subventricular zone (SVZa). We observed that precursors of the olfactory bulb responded to Notch signals by remaining quiescent and failing to give rise to differentiated progeny of any type, unlike cortical precursor cells, which generated glia instead of neurons. These data show that forebrain precursors vary in their response to Notch signals according to spatial and temporal cues, and that Notch signals influence the composition of forebrain regions by modulating the rate of proliferation of neural precursor cells.

scholarly journals Golgi localization of the LIN-2/7/10 complex points to a role in basolateral secretion of LET-23 EGFR in the C. elegans vulval precursor cells

Development ◽  
2021 ◽  
pp. dev.194167
Author(s):  
Kimberley D. Gauthier ◽  
Christian E. Rocheleau
Keyword(s):  
Cell Fate ◽  
Spatial Organization ◽  
Basolateral Membrane ◽  
Growth Factor Receptor ◽  
Precursor Cells ◽  
C Elegans ◽  
Receptor Localization ◽  
Epidermal Growth ◽  
Complex Forms

The evolutionarily conserved LIN-2 (CASK)/LIN-7 (Lin7A-C)/LIN-10 (APBA1) complex plays an important role in regulating spatial organization of membrane proteins and signaling components. In C. elegans, the complex is essential for development of the vulva by promoting the localization of the sole Epidermal Growth Factor Receptor (EGFR) orthologue, LET-23, to the basolateral membrane of the vulva precursor cells (VPCs) where it can specify the vulval cell fate. To understand how the LIN-2/7/10 complex regulates receptor localization, we determined its expression and localization during vulva development. We found that LIN-7 colocalizes with LET-23 EGFR at the basolateral membrane, whereas the LIN-2/7/10 complex colocalizes with LET-23 EGFR at cytoplasmic punctae, that mostly overlap with the Golgi. Furthermore, LIN-10 recruits LIN-2, which in turn recruits LIN-7. We demonstrate that the complex forms in vivo with particularly strong interaction and colocalization between LIN-2 and LIN-7 consistent with their forming a subcomplex. Thus, the LIN-2/7/10 complex forms on the Golgi where it likely targets LET-23 EGFR trafficking to the basolateral membrane rather than functioning as a tether.

scholarly journals Quantifying the correlation between spatially defined oxygen gradients and cell fate in an engineered three-dimensional culture model

2014 ◽  
Vol 11 (98) ◽  
pp. 20140501 ◽  
Author(s):  
Amir G. Ardakani ◽  
Umber Cheema ◽  
Robert A. Brown ◽  
Rebecca J. Shipley
Keyword(s):  
Cell Fate ◽  
Cellular Proliferation ◽  
Three Dimensional ◽  
Quantitative Information ◽  
Cell Number ◽  
Cellular Density ◽  
Spatially Resolved ◽  
Migratory Speed

A challenge in three-dimensional tissue culture remains the lack of quantitative information linking nutrient delivery and cellular distribution. Both in vivo and in vitro , oxygen is delivered by diffusion from its source (blood vessel or the construct margins). The oxygen level at a defined distance from its source depends critically on the balance of diffusion and cellular metabolism. Cells may respond to this oxygen environment through proliferation, death and chemotaxis, resulting in spatially resolved gradients in cellular density. This study extracts novel spatially resolved and simultaneous data on tissue oxygenation, cellular proliferation, viability and chemotaxis in three-dimensional spiralled, cellular collagen constructs. Oxygen concentration gradients drove preferential cellular proliferation rates and viability in the higher oxygen zones and induced chemotaxis along the spiral of the collagen construct; an oxygen gradient of 1.03 mmHg mm −1 in the spiral direction induced a mean migratory speed of 1015 μm day −1 . Although this movement was modest, it was effective in balancing the system to a stable cell density distribution, and provided insights into the natural cell mechanism for adapting cell number and activity to a prevailing oxygen regime.

Timing and pattern of cell fate restrictions in the neural crest lineage

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4351-4359 ◽  
Author(s):  
P.D. Henion ◽  
J.A. Weston
Keyword(s):  
Neural Crest ◽  
Cell Fate ◽  
Neural Tube ◽  
Neural Crest Cell ◽  
Precursor Cells ◽  
Cell Fates ◽  
Distinct Cell ◽  
Ventral Pathway ◽  
Neural Crest Cell Migration

The trunk neural crest of vertebrate embryos is a transient collection of precursor cells present along the dorsal aspect of the neural tube. These cells migrate on two distinct pathways and give rise to specific derivatives in precise embryonic locations. One group of crest cells migrates early on a ventral pathway and generates neurons and glial cells. A later-dispersing group migrates laterally and gives rise to melanocytes in the skin. These observations raise the possibility that the appearance of distinct derivatives in different embryonic locations is a consequence of lineage restrictions specified before or soon after the onset of neural crest cell migration. To test this notion, we have assessed when and in what order distinct cell fates are specified during neural crest development. We determined the proportions of different types of precursor cells in cultured neural crest populations immediately after emergence from the neural tube and at intervals as development proceeds. We found that the initial neural crest population was a heterogeneous mixture of precursors almost half of which generated single-phenotype clones. Distinct neurogenic and melanogenic sublineages were also present in the outgrowth population almost immediately, but melanogenic precursors dispersed from the neural tube only after many neurogenic precursors had already done so. A discrete fate-restricted neuronal precursor population was distinguished before entirely separate fate-restricted melanocyte and glial precursor populations were present, and well before initial neuronal differentiation. Taken together, our results demonstrate that lineage-restricted subpopulations constitute a major portion of the initial neural crest population and that neural crest diversification occurs well before overt differentiation by the asynchronous restriction of distinct cell fates. Thus, the different morphogenetic and differentiative behavior of neural crest subsets in vivo may result from earlier cell fate-specification events that generate developmentally distinct subpopulations that respond differentially to environmental cues.

scholarly journals Distribution of neurosensory progenitor pools during inner ear morphogenesis unveiled by cell lineage reconstruction

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Sylvia Dyballa ◽  
Thierry Savy ◽  
Philipp Germann ◽  
Karol Mikula ◽  
Mariana Remesikova ◽  
...  
Keyword(s):  
Inner Ear ◽  
Cell Fate ◽  
Functional Organization ◽  
Cell Lineage ◽  
Cell Types ◽  
Otic Vesicle ◽  
Neuronal Progenitor ◽  
Temporal Cues ◽  
Dynamic Map

Reconstructing the lineage of cells is central to understanding how the wide diversity of cell types develops. Here, we provide the neurosensory lineage reconstruction of a complex sensory organ, the inner ear, by imaging zebrafish embryos in vivo over an extended timespan, combining cell tracing and cell fate marker expression over time. We deliver the first dynamic map of early neuronal and sensory progenitor pools in the whole otic vesicle. It highlights the remodeling of the neuronal progenitor domain upon neuroblast delamination, and reveals that the order and place of neuroblasts’ delamination from the otic epithelium prefigure their position within the SAG. Sensory and non-sensory domains harbor different proliferative activity contributing distinctly to the overall growth of the structure. Therefore, the otic vesicle case exemplifies a generic morphogenetic process where spatial and temporal cues regulate cell fate and functional organization of the rudiment of the definitive organ.

scholarly journals EGF signaling promotes the lineage conversion of astrocytes into oligodendroglias

2021 ◽  
Author(s):  
Xinyu Liu ◽  
Lesi Xie ◽  
Jiao Li ◽  
Conghui Li ◽  
Kang Zheng ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Fate ◽  
Growth Factor Receptor ◽  
Transition Process ◽  
Precursor Cells ◽  
Epidermal Growth ◽  
Egf Signaling

Abstract Background The conversion of astrocytes activated by nerve injuries to oligodendrocytes is not only beneficial to axonal remyelination, but also helpful for reversal of glial scar. Recent studies have shown that Sox10 transcription factor can achieve this transdifferentiation process in collaboration with some unknown factors in the pathological microenvironment. The extracellular factors underlying the cell fate switching are not known. Methods Astrocytes were obtained from mouse cortical dissociation culture and purified by differential adherent properties. The lineage conversion of astrocytes into oligodendrocyte lineage cells was carried out by Sox10-expressing virus infection both in vitro and in vivo, meanwhile, epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) inhibitor Gefitinib were adopted to investigate the function of EGF signaling in this fate transition process. Pharmacological inhibition analyses were performed to examine the pathway connecting the EGF with the expression of oligodendrogenic genes and cell fate transdifferentiation. Results EGF treatment facilitated the Sox10-induced transformation of astrocytes to O4+ induced oligodendrocyte precursor cells (iOPCs) in vitro. The transdifferentiation of astrocytes to iOPCs went through two distinct but interconnected processes: (1) dedifferentiation of astrocytes to astrocyte precursor cells (APCs); (2) transformation of APCs to iOPCs, EGF signaling was involved in both processes. And EGF triggered astrocytes to express oligodendrogenic genes Olig1 and Olig2 by activating extracellular signal-regulated kinase 1 and 2 (Erk1/2) pathway. In addition, we discovered that EGF can enhance astrocyte transdifferentiation in injured spinal cord tissues. Conclusions These findings provide strong evidence that EGF facilitates the transdifferentiation of astrocytes to oligodendroglias, and suggest that targeting the EGF-EGFR-Erk1/2 signaling axis may represent a novel therapeutic strategy for myelin repair in injured central nervous system (CNS) tissues.

Potassium Currents in Precursor Cells Isolated From the Anterior Subventricular Zone of the Neonatal Rat Forebrain

1999 ◽  
Vol 81 (1) ◽  
pp. 95-102 ◽  
Author(s):  
R. R. Stewart ◽  
T. Zigova ◽  
M. B. Luskin
Keyword(s):  
Subventricular Zone ◽  
Action Potentials ◽  
Potassium Current ◽  
Potassium Currents ◽  
Precursor Cells ◽  
Neonatal Rat ◽  
Delayed Rectifier ◽  
Activation Time ◽  
Rat Forebrain ◽  
Anterior Subventricular Zone

Stewart, R. R., T. Zigova, and M. B. Luskin. Potassium currents in precursor cells isolated from the anterior subventricular zone of the neonatal rat forebrain. J. Neurophysiol. 81: 95–102, 1999. The progenitor cells from the anterior part of the neonatal subventricular zone, the SVZa, are unusual in that, although they undergo division, they have a neuronal phenotype. To characterize the electrophysiological properties of the SVZa precursor cells, recordings were made of potassium and sodium currents from SVZa cells that were removed from postnatal day 0–1 rats and cultured for 1 day. The properties of the delayed rectifier and A-type potassium currents were described by classical Hodgkin and Huxley analyses of activation and inactivation. In addition, cells were assessed under current clamp for their ability to generate action potentials. The A-type potassium current ( I K(A)) was completely inactivated at a holding potential of −50 mV. The remaining potassium current resembled the delayed rectifier current ( I K(DR)) in that it was blocked by tetraethylammonium (TEA; IC50 4.1 mM) and activated and inactivated slowly compared with I K(A). The conductance-voltage ( G- V) curve revealed that G increased continuously from 0.2 nS at −40 mV to a peak of 2.6 nS at +10 or +20 mV, and then decreased for voltages above +30 mV. Activation time constants were largest at −40 mV (∼11 ms) and smallest at 100 mV (∼1.5 ms). The properties of I K(A) were studied in the presence of 20 mM TEA, to block I K(DR), and from a holding potential of −15 mV, to inactivate both I K(DR) and I K(A). I K(A) was then allowed to recover from inactivation to negative potentials during 200- to 800-ms pulses. Recovery from inactivation was fastest at −130 mV (∼21 ms) and slowest at −90 mV (∼135 ms). Inactivation was voltage independent from −60 to +60 mV with a time constant of ∼15 ms. At steady state, I K(A) was half inactivated at −90 mV. G K(A) increased from 0.2 nS at −60 mV to a peak of 2.4 nS at +40 mV. Finally, the activation time constants ranged from ∼1.9 ms at −50 mV to 0.7 ms at +60 mV. The properties of I K(A) resembled those of I K(A) found in differentiating cerebellar granule neurons. Most SVZa cells had sodium currents (28/32 cells). However, in current clamp 11 of 12 cells were incapable of generating action potentials from voltages of −30 to −100 mV, suggesting that the available current densities were too low to support excitability.

scholarly journals Gender-specific effects of transthyretin on neural stem cell fate in the subventricular zone of the adult mouse

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Pieter Vancamp ◽  
Jean-David Gothié ◽  
Cristina Luongo ◽  
Anthony Sébillot ◽  
Karine Le Blay ◽  
...  
Keyword(s):  
Stem Cell ◽  
Choroid Plexus ◽  
Cell Fate ◽  
Neural Stem Cell ◽  
Subventricular Zone ◽  
Mrna Levels ◽  
Specific Effects ◽  
Gender Specific

AbstractChoroid plexus epithelial cells produce and secrete transthyretin (TTR). TTR binds and distributes thyroid hormone (TH) to brain cells via the cerebrospinal fluid. The adult murine subventricular zone (SVZ) is in close proximity to the choroid plexus. In the SVZ, TH determines neural stem cell (NSC) fate towards a neuronal or a glial cell. We investigated whether the loss of TTR also disrupted NSC fate choice. Our results show a decreased neurogenic versus oligodendrogenic balance in the lateroventral SVZ of Ttr knockout mice. This balance was also decreased in the dorsal SVZ, but only in Ttr knockout male mice, concomitant with an increased oligodendrocyte precursor density in the corpus callosum. Quantitative RTqPCR analysis following FACS-dissected SVZs, or marked-coupled microbeads sorting of in vitro neurospheres, showed elevated Ttr mRNA levels in neuronal cells, as compared to uncommitted precursor and glial cells. However, TTR protein was undetectable in vivo using immunostaining, and this despite the presence of Ttr mRNA-expressing SVZ cells. Altogether, our data demonstrate that TTR is an important factor in SVZ neuro- and oligodendrogenesis. They also reveal important gender-specific differences and spatial heterogeneity, providing new avenues for stimulating endogenous repair in neurodegenerative diseases.

scholarly journals Cell Progeny in the Olfactory Bulb after Targeting Specific Progenitors with Different UbC-StarTrack Approaches

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 305 ◽  
Author(s):  
Rebeca Sánchez-González ◽  
María Figueres-Oñate ◽  
Ana Cristina Ojalvo-Sanz ◽  
Laura López-Mascaraque
Keyword(s):  
Olfactory Bulb ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Phenotypic Variation ◽  
Subventricular Zone ◽  
Phenotypic Diversity ◽  
Neural Progenitors ◽  
Genetic Profile ◽  
Molecular Profiles

The large phenotypic variation in the olfactory bulb may be related to heterogeneity in the progenitor cells. Accordingly, the progeny of subventricular zone (SVZ) progenitor cells that are destined for the olfactory bulb is of particular interest, specifically as there are many facets of these progenitors and their molecular profiles remain unknown. Using modified StarTrack genetic tracing strategies, specific SVZ progenitor cells were targeted in E12 mice embryos, and the cell fate of these neural progenitors was determined in the adult olfactory bulb. This study defined the distribution and the phenotypic diversity of olfactory bulb interneurons from specific SVZ-progenitor cells, focusing on their spatial pallial origin, heterogeneity, and genetic profile.

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