Modulation of the notch signaling by Mash1 and Dlx1/2regulates sequential specification and differentiation of progenitor cell types in the subcortical telencephalon

Development ◽  
2002 ◽  
Vol 129 (21) ◽  
pp. 5029-5040 ◽  
Author(s):  
Kyuson Yun ◽  
Seth Fischman ◽  
Jane Johnson ◽  
Martin Hrabe de Angelis ◽  
Gerry Weinmaster ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Notch Signaling ◽  
Cell Fate ◽  
Progenitor Cell ◽  
Cell Types ◽  
Cell Fate Specification ◽  
Early Neurogenesis ◽  
Molecular Phenotypes ◽  
Postmitotic Cell ◽  
Homeobox Transcription Factors

Notch signaling has a central role in cell fate specification and differentiation. We provide evidence that the Mash1 (bHLH) andDlx1 and Dlx2 (homeobox) transcription factors have complementary roles in regulating Notch signaling, which in turn mediates the temporal control of subcortical telencephalic neurogenesis in mice. We defined progressively more mature subcortical progenitors (P1, P2 and P3) through their combinatorial expression of MASH1 and DLX2, as well as the expression of proliferative and postmitotic cell markers at E10.5-E11.5. In the absence ofMash1, Notch signaling is greatly reduced and `early' VZ progenitors(P1 and P2) precociously acquire SVZ progenitor (P3) properties. Comparing the molecular phenotypes of the delta-like 1 and Mash1 mutants, suggests that Mash1 regulates early neurogenesis through Notch-and Delta-dependent and -independent mechanisms. While Mash1 is required for early neurogenesis (E10.5), Dlx1 and Dlx2 are required to downregulate Notch signaling during specification and differentiation steps of `late' progenitors (P3). We suggest that alternate cell fate choices in the developing telencephalon are controlled by coordinated functions of bHLH and homeobox transcription factors through their differential affects on Notch signaling.

Amifostine Inhibits Hematopoietic Progenitor Cell Apoptosis by Activating NF-κB/Rel Transcription Factors

Blood ◽  
1999 ◽  
Vol 94 (12) ◽  
pp. 4060-4066 ◽  
Author(s):  
Maria Fiammetta Romano ◽  
Annalisa Lamberti ◽  
Rita Bisogni ◽  
Corrado Garbi ◽  
Antonio M. Pagnano ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Apoptosis ◽  
Progenitor Cell ◽  
Cell Types ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor ◽  
Mobility Shift ◽  
Human Cord Blood ◽  
Mobility Shift Assay ◽  
Induced Apoptosis

Abstract We investigated the involvement of NF-κB/Rel transcription factors that reportedly can inhibit apoptosis in various cell types in the antiapoptotic mechanism of the cytoprotectant amifostine. In the nontumorigenic murine myeloid progenitor 32D cells incubated with amifostine, we detected a reduction of the IκB cytoplasmic levels by Western blotting and a raising of nuclear NF-κB/Rel complexes by electrophoretic mobility shift assay. Amifostine inhibited by more than 30% the growth factor deprivation-induced apoptosis, whereas its effect failed when we blocked the NF-κB/Rel activity with an NF-κB/Rel-binding phosphorothioate decoy oligodeoxynucleotide. In human cord blood CD34+ cells, the NF-κB/Rel p65 subunit was detectable (using immunofluorescence analysis) mainly in the cytoplasm in the absence of amifostine, whereas its presence was appreciable in the nuclei of cells incubated with the cytoprotectant. In 4 CD34+ samples incubated for 3 days in cytokine-deficient conditions, cell apoptosis was reduced by more than 30% in the presence of amifostine (or amifostine plus a control oligo); the effect of amifostine was abolished in cultures with the decoy oligo. These findings indicate that the inhibition of hematopoietic progenitor cell apoptosis by amifostine requires the induction of NF-κB/Rel factors and that the latter can therefore exert an antiapoptotic activity in the hematopoietic progenitor cell compartment. Furthermore, the identification of this specific mechanism underlying the survival-promoting activity of amifostine lends support to the possible use of this agent in apoptosis-related pathologies, such as myelodysplasias.

Serrate and Notch specify cell fates in the heart field by suppressing cardiomyogenesis

Development ◽  
2000 ◽  
Vol 127 (17) ◽  
pp. 3865-3876
Author(s):  
M.S. Rones ◽  
K.A. McLaughlin ◽  
M. Raffin ◽  
M. Mercola
Keyword(s):  
Gene Expression ◽  
Notch Signaling ◽  
Cell Fate ◽  
Notch Pathway ◽  
Cell Types ◽  
Myocardial Cell ◽  
Dominant Negative ◽  
Cell Fates ◽  
Cell Fate Decisions ◽  
Heart Field

Notch signaling mediates numerous developmental cell fate decisions in organisms ranging from flies to humans, resulting in the generation of multiple cell types from equipotential precursors. In this paper, we present evidence that activation of Notch by its ligand Serrate apportions myogenic and non-myogenic cell fates within the early Xenopus heart field. The crescent-shaped field of heart mesoderm is specified initially as cardiomyogenic. While the ventral region of the field forms the myocardial tube, the dorsolateral portions lose myogenic potency and form the dorsal mesocardium and pericardial roof (Raffin, M., Leong, L. M., Rones, M. S., Sparrow, D., Mohun, T. and Mercola, M. (2000) Dev. Biol., 218, 326–340). The local interactions that establish or maintain the distinct myocardial and non-myocardial domains have never been described. Here we show that Xenopus Notch1 (Xotch) and Serrate1 are expressed in overlapping patterns in the early heart field. Conditional activation or inhibition of the Notch pathway with inducible dominant negative or active forms of the RBP-J/Suppressor of Hairless [Su(H)] transcription factor indicated that activation of Notch feeds back on Serrate1 gene expression to localize transcripts more dorsolaterally than those of Notch1, with overlap in the region of the developing mesocardium. Moreover, Notch pathway activation decreased myocardial gene expression and increased expression of a marker of the mesocardium and pericardial roof, whereas inhibition of Notch signaling had the opposite effect. Activation or inhibition of Notch also regulated contribution of individual cells to the myocardium. Importantly, expression of Nkx2. 5 and Gata4 remained largely unaffected, indicating that Notch signaling functions downstream of heart field specification. We conclude that Notch signaling through Su(H) suppresses cardiomyogenesis and that this activity is essential for the correct specification of myocardial and non-myocardial cell fates.

scholarly journals Scabrous overexpression in the eye affects R3/R4 cell fate specification and inhibits notch signaling

2015 ◽  
Vol 245 (2) ◽  
pp. 166-174 ◽  
Author(s):  
Verónica Muñoz-Soriano ◽  
Diego Santos ◽  
Fabrice C. Durupt ◽  
Sandra Casani ◽  
Nuria Paricio
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Cell Fate Specification ◽  
Fate Specification

scholarly journals Anxa4 mediated airway progenitor cell migration promotes distal epithelial cell fate specification

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Kewu Jiang ◽  
Zan Tang ◽  
Juan Li ◽  
Fengchao Wang ◽  
Nan Tang
Keyword(s):  
Cell Migration ◽  
Epithelial Cell ◽  
Cell Fate ◽  
Progenitor Cell ◽  
Cell Fate Specification ◽  
Fate Specification

Amifostine Inhibits Hematopoietic Progenitor Cell Apoptosis by Activating NF-κB/Rel Transcription Factors

Blood ◽  
1999 ◽  
Vol 94 (12) ◽  
pp. 4060-4066 ◽  
Author(s):  
Maria Fiammetta Romano ◽  
Annalisa Lamberti ◽  
Rita Bisogni ◽  
Corrado Garbi ◽  
Antonio M. Pagnano ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Apoptosis ◽  
Progenitor Cell ◽  
Cell Types ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor ◽  
Mobility Shift ◽  
Human Cord Blood ◽  
Mobility Shift Assay ◽  
Induced Apoptosis

We investigated the involvement of NF-κB/Rel transcription factors that reportedly can inhibit apoptosis in various cell types in the antiapoptotic mechanism of the cytoprotectant amifostine. In the nontumorigenic murine myeloid progenitor 32D cells incubated with amifostine, we detected a reduction of the IκB cytoplasmic levels by Western blotting and a raising of nuclear NF-κB/Rel complexes by electrophoretic mobility shift assay. Amifostine inhibited by more than 30% the growth factor deprivation-induced apoptosis, whereas its effect failed when we blocked the NF-κB/Rel activity with an NF-κB/Rel-binding phosphorothioate decoy oligodeoxynucleotide. In human cord blood CD34+ cells, the NF-κB/Rel p65 subunit was detectable (using immunofluorescence analysis) mainly in the cytoplasm in the absence of amifostine, whereas its presence was appreciable in the nuclei of cells incubated with the cytoprotectant. In 4 CD34+ samples incubated for 3 days in cytokine-deficient conditions, cell apoptosis was reduced by more than 30% in the presence of amifostine (or amifostine plus a control oligo); the effect of amifostine was abolished in cultures with the decoy oligo. These findings indicate that the inhibition of hematopoietic progenitor cell apoptosis by amifostine requires the induction of NF-κB/Rel factors and that the latter can therefore exert an antiapoptotic activity in the hematopoietic progenitor cell compartment. Furthermore, the identification of this specific mechanism underlying the survival-promoting activity of amifostine lends support to the possible use of this agent in apoptosis-related pathologies, such as myelodysplasias.

Notch signaling in the pancreas: patterning and cell fate specification

2012 ◽  
Vol 2 (4) ◽  
pp. 531-544 ◽  
Author(s):  
Solomon Afelik ◽  
Jan Jensen
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Cell Fate Specification ◽  
Fate Specification

scholarly journals RBP-Jκ-Dependent Notch Signaling Is Dispensable for Mouse Early Embryonic Development

2006 ◽  
Vol 26 (13) ◽  
pp. 4769-4774 ◽  
Author(s):  
Céline Souilhol ◽  
Sarah Cormier ◽  
Kenji Tanigaki ◽  
Charles Babinet ◽  
Michel Cohen-Tannoudji
Keyword(s):  
Embryonic Development ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Preimplantation Embryos ◽  
Cell Fate Specification ◽  
Fate Specification ◽  
Evolutionarily Conserved

ABSTRACT The Notch signaling pathway is an evolutionarily conserved signaling system which has been shown to be essential in cell fate specification and in numerous aspects of embryonic development in all metazoans thus far studied. We recently demonstrated that several components of the Notch signaling pathway, including the four Notch receptors and their five ligands known in mammals, are expressed in mouse oocytes, in mouse preimplantation embryos, or both. This suggested a possible implication of the Notch pathway in the first cell fate specification of the dividing mouse embryo, which results in the formation of the blastocyst. To address this issue directly, we generated zygotes in which both the maternal and the zygotic expression of Rbpsuh, a key element of the core Notch signaling pathway, were abrogated. We find that such zygotes give rise to blastocysts which implant and develop normally. Nevertheless, after gastrulation, these embryos die around midgestation, similarly to Rbpsuh-null mutants. This demonstrates that the RBP-Jκ-dependent pathway, otherwise called the canonical Notch pathway, is dispensable for blastocyst morphogenesis and the establishment of the three germ layers, ectoderm, endoderm, and mesoderm. These results are discussed in the light of recent observations which have challenged this conclusion.

scholarly journals Glucocorticoid agonists enhance retinal stem cell self-renewal and proliferation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kenneth N. Grisé ◽  
Nelson X. Bautista ◽  
Krystal Jacques ◽  
Brenda L. K. Coles ◽  
Derek van der Kooy
Keyword(s):  
Cell Fate ◽  
Progenitor Cell ◽  
Cell Types ◽  
Retinal Cell ◽  
Ciliary Epithelium ◽  
Cell Transplant ◽  
Self Renewal ◽  
Synthetic Glucocorticoid

Abstract Background Adult mammalian retinal stem cells (RSCs) readily proliferate, self-renew, and generate progeny that differentiate into all retinal cell types in vitro. RSC-derived progeny can be induced to differentiate into photoreceptors, making them a potential source for retinal cell transplant therapies. Despite their proliferative propensity in vitro, RSCs in the adult mammalian eye do not proliferate and do not have a regenerative response to injury. Thus, identifying and modulating the mechanisms that regulate RSC proliferation may enhance the capacity to produce RSC-derived progeny in vitro and enable RSC activation in vivo. Methods Here, we used medium-throughput screening to identify small molecules that can expand the number of RSCs and their progeny in culture. In vitro differentiation assays were used to assess the effects of synthetic glucocorticoid agonist dexamethasone on RSC-derived progenitor cell fate. Intravitreal injections of dexamethasone into adult mouse eyes were used to investigate the effects on endogenous RSCs. Results We discovered that high-affinity synthetic glucocorticoid agonists increase RSC self-renewal and increase retinal progenitor proliferation up to 6-fold without influencing their differentiation in vitro. Intravitreal injection of synthetic glucocorticoid agonist dexamethasone induced in vivo proliferation in the ciliary epithelium—the niche in which adult RSCs reside. Conclusions Together, our results identify glucocorticoids as novel regulators of retinal stem and progenitor cell proliferation in culture and provide evidence that GCs may activate endogenous RSCs.

scholarly journals Foxi1 inactivation rescues loss of principal cell fate selection in Hes1-deficient kidneys but does not ensure maintenance of principal cell gene expression

2019 ◽  
Author(s):  
Malini Mukherjee ◽  
Jennifer DeRiso ◽  
Madhusudhana Janga ◽  
Eric Fogarty ◽  
Kameswaran Surendran
Keyword(s):  
Gene Expression ◽  
Notch Signaling ◽  
Cell Fate ◽  
Collecting Duct ◽  
Cell Types ◽  
Principal Cell ◽  
Intercalated Cell ◽  
Collecting Ducts ◽  
Cell Gene Expression ◽  
Cell Gene

AbstractThe distal nephron and collecting duct segments of the mammalian kidney consist of intercalated cell types intermingled among principal cell types. Notch signaling ensures that a sufficient number of cells select a principal instead of an intercalated cell fate. However, the precise mechanisms by which Notch signaling patterns the distal nephron and collecting duct cell fates is unknown. Here we observed that Hes1, a direct target of Notch signaling pathway, is required within the mouse developing collecting ducts for repression of Foxi1 expression, an essential intercalated cell specific transcription factor. Interestingly, inactivation of Foxi1 in Hes1-deficient collecting ducts rescues the deficiency in principal cell fate selection, overall urine concentrating deficiency, and reduces the occurrence of hydronephrosis. However, Foxi1 inactivation does not rescue the reduction in expression of all principal cell genes in the Hes1-deficient kidney collecting duct cells that select the principal cell fate. Additionally, suppression of Notch/Hes1 signaling in mature principal cells reduces principal cell gene expression without activating Foxi1. We conclude that Hes1 is a Notch signaling target that is essential for normal patterning of the collecting ducts with intermingled cell types by repressing Foxi1, and for maintenance of principal cell gene expression independent of repressing Foxi1.

Sign in / Sign up

Export Citation Format

Share Document