Lithium inhibits morphogenesis of the nervous system but not neuronal differentiation in Xenopus laevis

Development ◽  
1987 ◽  
Vol 99 (3) ◽  
pp. 353-370 ◽  
Author(s):  
L.J. Breckenridge ◽  
R.L. Warren ◽  
A.E. Warner

Xenopus embryos treated with 100 mM-lithium from the 2- to 4-cell stage to the early blastula stage (4h) failed to neurulate and developed without a discernible anteroposterior axis. The internal structure of defective embryos was grossly disorganized, but immunohistochemical staining with cell-type-specific antibodies revealed differentiated nerve and muscle cells. Quantitative assay in tissue cultures from control and acutely abnormal lithium-treated embryos showed that neural differentiation was enhanced and muscle differentiation unaffected. The embryos took up about 0.5 mM-lithium at threshold, maximal effects resulted at 2–3 mM. Most of the lithium was extruded from the cells into the blastocoel fluid, where lithium reached 17 mM. The threshold intracellular concentration was about 150 microM. Lithium uptake rose steeply as the osmotic/ionic strength of the bathing medium increased. Sodium, potassium and lithium were equally able to increase the permeability of the embryo. However, sodium ions enhanced, while potassium ions interfered with, the uptake of lithium. Treatment with lithium at progressively later stages reduced the developmental defects and neural differentiation returned to normal levels. The uptake of lithium did not decline concomitantly. We conclude that lithium does not inhibit neural induction, but interferes with dorsal patterning. The sensitivity of the embryo to lithium is determined by developmental stage. The very low, effective intracellular concentrations may be important in understanding the mechanism of lithium-generated defects.

2019 ◽  
Author(s):  
Eriko Shimada ◽  
Yusuke Tsuruwaka

Various cancer cells are known to show neural differentiation. Adrenocortical carcinoma (ACC) is a rare and frequently aggressive tumor originating in the cortex of the adrenal gland. Early diagnosis of ACC is challenging due to a lot of unknown aspects such as cell characteristics in a rare cancer. In the present study, morphological features were examined in the adrenal cortex carcinoma cells SW-13 as an initial candidate, which were exposed to neural differentiation condition. SW-13 cells treated with the neural induction supplement showed neural-like differentiation with elongated filaments. It was suggested that SW-13 cells had neural differentiation potential and could be a research tool to elucidate the cell characteristics in future ACC studies.


2000 ◽  
Vol 113 (19) ◽  
pp. 3519-3529 ◽  
Author(s):  
C. Leclerc ◽  
S.E. Webb ◽  
C. Daguzan ◽  
M. Moreau ◽  
A.L. Miller

Through the injection of f-aequorin (a calcium-sensitive bioluminescent reporter) into the dorsal micromeres of 8-cell stage Xenopus laevis embryos, and the use of a Photon Imaging Microscope, distinct patterns of calcium signalling were visualised during the gastrulation period. We present results to show that localised domains of elevated calcium were observed exclusively in the anterior dorsal part of the ectoderm, and that these transients increased in number and amplitude between stages 9 to 11, just prior to the onset of neural induction. During this time, however, no increase in cytosolic free calcium was observed in the ventral ectoderm, mesoderm or endoderm. The origin and role of these dorsal calcium-signalling patterns were also investigated. Calcium transients require the presence of functional L-type voltage-sensitive calcium channels. Inhibition of channel activation from stages 8 to 14 with the specific antagonist R(+)BayK 8644 led to a complete inhibition of the calcium transients during gastrulation and resulted in severe defects in the subsequent formation of the anterior nervous system. BayK treatment also led to a reduction in the expression of Zic3 and geminin in whole embryos, and of NCAM in noggin-treated animal caps. The possible role of calcium transients in regulating developmental gene expression is discussed.


Development ◽  
1989 ◽  
Vol 107 (4) ◽  
pp. 785-791 ◽  
Author(s):  
E.A. Jones ◽  
H.R. Woodland

A monoclonal antibody, 2G9, has been identified and characterised as a marker of neural differentiation in Xenopus. The epitope is present throughout the adult central nervous system and in peripheral nerves. Staining is first detected in embryos at stage 21 in the thoracic region. By stage 29 it stains the whole central nervous system, except the tail tip. The epitope is present in a 65K Mr protein, and includes sialic acid. The antibody also reacts with neural tissue in mice and axolotls and newts. 2G9 was used to show that both notochord and somites are capable of neural induction, and the stimulus is present as late as stage 22. Attempts to demonstrate the induction of nervous system by developing nervous system (homoiogenetic induction) were unsuccessful. The view that the lateral extent of the nervous system might be determined by that of the inductive stimulus is discussed. Neural induction was detected as early as stage 10 and occurs in embryos without gastrulation and without cell division from stage 7 1/2.


Development ◽  
1995 ◽  
Vol 121 (3) ◽  
pp. 721-730 ◽  
Author(s):  
S.E. Witta ◽  
V.R. Agarwal ◽  
S.M. Sato

XIPOU 2, a member of the class III POU domain family, is expressed initially in Spemann's organizer, and later, in discrete regions of the developing nervous system in Xenopus laevis. XIPOU 2 may act downstream from initial neural induction events, since it is activated by the neural inducer, noggin. To determine if XIPOU 2 participates in the early events of neurogenesis, synthetic mRNA was microinjected into specific blastomeres of the 32-cell stage embryo. Misexpression of XIPOU 2 in the epidermis causes a direct switch in cell fate from an epidermal to a neuronal phenotype. In the absence of mesoderm induction, XIPOU 2 has the ability to induce a neuronal phenotype in uncommitted ectoderm. These data demonstrate the potential of XIPOU 2 to act as a master regulator of neurogenesis.


Development ◽  
2000 ◽  
Vol 127 (4) ◽  
pp. 791-800 ◽  
Author(s):  
M. Kishi ◽  
K. Mizuseki ◽  
N. Sasai ◽  
H. Yamazaki ◽  
K. Shiota ◽  
...  

From early stages of development, Sox2-class transcription factors (Sox1, Sox2 and Sox3) are expressed in neural tissues and sensory epithelia. In this report, we show that Sox2 function is required for neural differentiation of early Xenopus ectoderm. Microinjection of dominant-negative forms of Sox2 (dnSox2) mRNA inhibits neural differentiation of animal caps caused by attenuation of BMP signals. Expression of dnSox2 in developing embryos suppresses expression of N-CAM and regional neural markers. We have analyzed temporal requirement of Sox2-mediated signaling by using an inducible dnSox2 construct fused to the ligand-binding domain of the glucocorticoid receptor. Attenuation of Sox2 function both from the late blastula stage and from the late gastrula stage onwards causes an inhibition of neural differentiation in animal caps and in whole embryos. Additionally, dnSox2-injected cells that fail to differentiate into neural tissues are not able to adopt epidermal cell fate. These data suggest that Sox2-class genes are essential for early neuroectoderm cells to consolidate their neural identity during secondary steps of neural differentiation.


Zygote ◽  
1999 ◽  
Vol 8 (S1) ◽  
pp. S42-S43 ◽  
Author(s):  
Tetsuya Kominami

Sea urchin pluteus larvae contain dozens of pigment cells in their ectoderm. These pigment cells are the descendants of the veg2 blastomeres of the 60-cell stage embryo. According to the fate map made by Ruffins and Ettensohn, the prospective pigment cells occupy the central region of the vegetal plate. Most of these prospective pigment cells exclusively give rise to pigment cells. Therefore, specification of the pigment cell lineage should occur at some point between the 60-cell and mesenchyme blastula stage. However, the detailed process of the specification of the pigment lineage is unknown.When are pigment cells specified? Are cell interactions necessary for the specification? Do founder cells exist? To answer these questions, I treated embryos with Ca2+-free seawater during the cleavage stage and examined the number of pigment cells observed in pluteus larvae. Treatment at 5.5–8.5 h and especially 7.5–10.5 h postfertilisation markedly reduced the number of pigment cells. The decrease was statistically significant. On the other hand, the treatment at 3.5–6.5 h or 9.5–12.5 h never reduced the number of pigment cells. By examining the frequency of the appearance of embryos whose numbers of pigment cells were less than 20, it was also found that the numbers of pigment cells were frequently in multiples of 4. Embryos having 4, 8, 12, 16 and 20 pigment cells were more frequently observed. Statistics indicated that the frequency of appearance was not random. These results indicated that cell contacts are necessary for the specification of pigment cells and that the specification occurs from 7 to 10 h postfertilisation. The results also suggest that the founder cells, if they exist, divide twice before they differentiate into pigment cells.


2019 ◽  
Vol 21 (Supplement_2) ◽  
pp. ii64-ii64
Author(s):  
Alison Parisian ◽  
Tomoyuki Koga ◽  
Frank Furnari

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Sujeong Jang ◽  
Jong-Seong Park ◽  
Han-Seong Jeong

Stem cells are a powerful resource for cell-based transplantation therapies, but understanding of stem cell differentiation at the molecular level is not clear yet. We hypothesized that the Wnt pathway controls stem cell maintenance and neural differentiation. We have characterized the transcriptional expression of Wnt during the neural differentiation of hADSCs. After neural induction, the expressions of Wnt2, Wnt4, and Wnt11 were decreased, but the expression of Wnt5a was increased compared with primary hADSCs in RT-PCR analysis. In addition, the expression levels of most Fzds and LRP5/6 ligand were decreased, but not Fzd3 and Fzd5. Furthermore, Dvl1 and RYK expression levels were downregulated in NI-hADSCs. There were no changes in the expression of ß-catenin and GSK3ß. Interestingly, Wnt5a expression was highly increased in NI-hADSCs by real time RT-PCR analysis and western blot. Wnt5a level was upregulated after neural differentiation and Wnt3, Dvl2, and Naked1 levels were downregulated. Finally, we found that the JNK expression was increased after neural induction and ERK level was decreased. Thus, this study shows for the first time how a single Wnt5a ligand can activate the neural differentiation pathway through the activation of Wnt5a/JNK pathway by binding Fzd3 and Fzd5 and directing Axin/GSK-3ß in hADSCs.


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