scholarly journals Generation of the squamous epithelial roof of the 4th ventricle

2018 ◽  
Author(s):  
Florent Campo-Paysaa ◽  
Jonathan DW Clarke ◽  
Richard JT Wingate
Keyword(s):  
Cell Fate ◽  
Squamous Epithelium ◽  
De Novo ◽  
Dorsal Midline ◽  
Direct Transformation ◽  
Squamous Cells ◽  
Roof Plate ◽  
The Veil ◽  
Rhombic Lip ◽  
4Th Ventricle

SummaryWe use the transparency of zebrafish embryos to reveal the de novo generation of a simple squamous epithelium and identify the cellular architecture in the epithelial transition zone that ties this squamous epithelium to the columnar neuroepithelium within the embryo’s brain. The simple squamous epithelium of the rhombencephalic roof plate is pioneered by distinct mesenchymal cells at the dorsal midline of the neural tube. Subsequently a progenitor zone is established at the interface between columnar epithelium of the rhombic lip and the expanding squamous epithelium of the roof plate. Surprisingly this interface consists of a single progenitor cell type that we have named the veil cell. Veil cells express gdf6a and constitute a lineage restricted stem zone that generates the squamous roof plate by direct transformation and asymmetrically fated divisions. Experimental restriction of roof plate expansion leads to extrusion of veil cell daughters and squamous cells, suggesting veil cell fate is regulated by the space available for roof plate growth.

scholarly journals Generation of the squamous epithelial roof of the 4th ventricle

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Florent Campo-Paysaa ◽  
Jonathan DW Clarke ◽  
Richard JT Wingate
Keyword(s):  
Cell Fate ◽  
Squamous Epithelium ◽  
De Novo ◽  
Dorsal Midline ◽  
Direct Transformation ◽  
Squamous Cells ◽  
Roof Plate ◽  
The Veil ◽  
Rhombic Lip ◽  
4Th Ventricle

We use the transparency of zebrafish embryos to reveal the de novo generation of a simple squamous epithelium and identify the cellular architecture in the epithelial transition zone that ties this squamous epithelium to the columnar neuroepithelium within the embryo's brain. The simple squamous epithelium of the rhombencephalic roof plate is pioneered by distinct mesenchymal cells at the dorsal midline of the neural tube. Subsequently, a progenitor zone is established at the interface between columnar epithelium of the rhombic lip and the expanding squamous epithelium of the roof plate. Surprisingly, this interface consists of a single progenitor cell type that we have named the veil cell. Veil cells express gdf6a and constitute a lineage restricted stem zone that generates the squamous roof plate by direct transformation and asymmetrically fated divisions. Experimental restriction of roof plate expansion leads to extrusion of veil cell daughters and squamous cells, suggesting veil cell fate is regulated by the space available for roof plate growth.

scholarly journals The specification of noradrenergic locus coeruleus (LC) neurones depends on bone morphogenetic proteins (BMPs)

Development ◽  
2002 ◽  
Vol 129 (4) ◽  
pp. 983-991 ◽  
Author(s):  
Astrid Vogel-Höpker ◽  
Hermann Rohrer
Keyword(s):  
Transcription Factors ◽  
Locus Coeruleus ◽  
Bone Morphogenetic Proteins ◽  
Chick Embryos ◽  
Dorsal Midline ◽  
Neural Crest Development ◽  
Roof Plate ◽  
Rhombic Lip ◽  
The Brain

The role of BMPs in the development of the major noradrenergic centre of the brain, the locus coeruleus (LC), was investigated. LC generation is reflected by initial expression of the transcription factors Phox2a and Phox2b in dorsal rhombomere1 (r1), followed by expression of dopamine-β-hydroxylase and tyrosine hydroxylase. Bmp5 is expressed in the dorsal neuroepithelium in proximity to Phox2-expressing cells. BMP inhibition in stage 10 chick embryos resulted in the lack of LC neurones or in their generation at the dorsal midline, and loss of roof plate and rhombic lip, but it did not affect neural crest development. These results reveal late essential BMP functions in the specification of dorsal neuronal phenotypes in r1, including LC neurones, and in the development of dorsal midline structures.

A regulatory network of microRNAs confers lineage commitment during early developmental trajectories of B and T lymphocytes

2021 ◽  
Vol 118 (46) ◽  
pp. e2104297118
Author(s):  
Sameena Nikhat ◽  
Anurupa D. Yadavalli ◽  
Arpita Prusty ◽  
Priyanka K. Narayan ◽  
Dasaradhi Palakodeti ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Lymphocytes ◽  
Cell Fate ◽  
T Lymphocyte ◽  
De Novo ◽  
Gene Expression Pattern ◽  
Lymphocyte Development ◽  
Motif Analysis ◽  
Differentiation Potential ◽  
B And T Lymphocytes

The commitment of hematopoietic multipotent progenitors (MPPs) toward a particular lineage involves activation of cell type–specific genes and silencing of genes that promote alternate cell fates. Although the gene expression programs of early–B and early–T lymphocyte development are mutually exclusive, we show that these cell types exhibit significantly correlated microRNA (miRNA) profiles. However, their corresponding miRNA targetomes are distinct and predominated by transcripts associated with natural killer, dendritic cell, and myeloid lineages, suggesting that miRNAs function in a cell-autonomous manner. The combinatorial expression of miRNAs miR-186-5p, miR-128-3p, and miR-330-5p in MPPs significantly attenuates their myeloid differentiation potential due to repression of myeloid-associated transcripts. Depletion of these miRNAs caused a pronounced de-repression of myeloid lineage targets in differentiating early–B and early–T cells, resulting in a mixed-lineage gene expression pattern. De novo motif analysis combined with an assay of promoter activities indicates that B as well as T lineage determinants drive the expression of these miRNAs in lymphoid lineages. Collectively, we present a paradigm that miRNAs are conserved between developing B and T lymphocytes, yet they target distinct sets of promiscuously expressed lineage-inappropriate genes to suppress the alternate cell-fate options. Thus, our studies provide a comprehensive compendium of miRNAs with functional implications for B and T lymphocyte development.

scholarly journals Natural loss of function of ephrin-B3 shapes spinal flight circuitry in birds

2021 ◽  
Vol 7 (24) ◽  
pp. eabg5968
Author(s):  
Baruch Haimson ◽  
Oren Meir ◽  
Reut Sudakevitz-Merzbach ◽  
Gerard Elberg ◽  
Samantha Friedrich ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mutant Mouse ◽  
Loss Of Function ◽  
Dorsal Midline ◽  
Roof Plate ◽  
Embryonic Spinal Cord ◽  
Guidance Molecule

Flight in birds evolved through patterning of the wings from forelimbs and transition from alternating gait to synchronous flapping. In mammals, the spinal midline guidance molecule ephrin-B3 instructs the wiring that enables limb alternation, and its deletion leads to synchronous hopping gait. Here, we show that the ephrin-B3 protein in birds lacks several motifs present in other vertebrates, diminishing its affinity for the EphA4 receptor. The avian ephrin-B3 gene lacks an enhancer that drives midline expression and is missing in galliforms. The morphology and wiring at brachial levels of the chicken embryonic spinal cord resemble those of ephrin-B3 null mice. Dorsal midline decussation, evident in the mutant mouse, is apparent at the chick brachial level and is prevented by expression of exogenous ephrin-B3 at the roof plate. Our findings support a role for loss of ephrin-B3 function in shaping the avian brachial spinal cord circuitry and facilitating synchronous wing flapping.

scholarly journals p38-MAPK mediated rRNA processing and translation regulation enables PrE differentiation during mouse blastocyst maturation

2020 ◽  
Author(s):  
Pablo Bora ◽  
Lenka Gahurova ◽  
Tomáš Mašek ◽  
Andrea Hauserova ◽  
David Potěšil ◽  
...  
Keyword(s):  
Cell Fate ◽  
P38 Mapk ◽  
Ribosomal Proteins ◽  
De Novo ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Translation Regulation ◽  
Placental Development ◽  
Mapk Activity ◽  
Live Embryo

AbstractBackgroundp38-MAPKs are stress-activated kinases necessary for placental development and nutrient and oxygen transfer during murine post-implantation development. In preimplantation development, p38-MAPK activity is required for blastocyst formation. Additionally, we have previously reported its role in regulating specification of inner cell mass (ICM) towards primitive endoderm (PrE), although a comprehensive mechanistic understanding is currently limited. Adopting live embryo imaging, proteomic and transcriptomic approaches, we report experimental data that directly address this deficit.ResultsChemical inhibition of p38-MAPK activity during blastocyst maturation causes impaired blastocyst cavity expansion, most evident between the third and tenth hours post inhibition onset. We identify an overlapping minimal early blastocyst maturation window of p38-MAPKi inhibition (p38-MAPKi) sensitivity, that is sufficient to impair PrE cell fate by the late blastocyst (E4.5) stage. Comparative proteomic analyses reveal substantial downregulation of ribosomal proteins, the mRNA transcripts of which are also significantly upregulated. Ontological analysis of the differentially expressed transcriptome during this developmental period reveals “translation” related gene transcripts as being most significantly, yet transiently, affected by p38-MAPKi. Moreover, combined assays consistently report concomitant reductions in de novo translation that are associated with accumulation of unprocessed rRNA precursors. Using a phosphoproteomic approach, ± p38-MAPKi, we identified Mybpp1a, an rRNA transcription and processing regulator gene, as a potential p38-MAPK effector. We report that siRNA mediated clonal knockdown of Mybpp1a is associated with significantly diminished PrE contribution. Lastly, we show that defective PrE specification caused by p38-MAPKi (but not MEK/ERK signalling inhibition) can be partially rescued by activating the archetypal mTOR mediated translation regulatory pathway.ConclusionsActivated p38-MAPK controls blastocyst maturation in an early and distinctly transient developmental window by regulating gene functionalities related to translation, that creates a permissive environment for appropriate specification of ICM cell fate.

De novo induction of the organizer and formation of the primitive streak in an experimental model of notochord reconstitution in avian embryos

Development ◽  
1998 ◽  
Vol 125 (2) ◽  
pp. 201-213 ◽  
Author(s):  
S. Yuan ◽  
G.C. Schoenwolf
Keyword(s):  
Cell Fate ◽  
De Novo ◽  
Primitive Streak ◽  
Model System ◽  
Floor Plate ◽  
Avian Embryos ◽  
New Information ◽  
Derivatives Of ◽  
Novel Model ◽  
Neurula Stage

We have developed a model system for analyzing reconstitution of the notochord using cultured blastoderm isolates lacking Hensen's node and the primitive streak. Despite lacking normal notochordal precursor cells, the notochord still forms in these isolates during the 36 hours in culture. Reconstitution of the notochord involves an inducer, which acts upon a responder, thereby inducing a reconstituted notochord. To better understand the mechanism of notochord reconstitution, we asked whether formation of the notochord in the model system was preceded by reconstitution of Hensen's node, the organizer of the avian neuraxis. Our results show not only that a functional organizer is reconstituted, but that this organizer is induced from the responder. First, fate mapping reveals that the responder forms a density, morphologically similar to Hensen's node, during the first 10–12 hours in culture, and that this density expresses typical markers of Hensen's node. Second, the density, when fate mapped or when labeled and transplanted in place of Hensen's node, forms typical derivatives of Hensen's node such as endoderm, notochord and the floor plate of the neural tube. Third, the density, when transplanted to an ectopic site, induces a secondary neuraxis, identical to that induced by Hensen's node. And fourth, the density acts as a suppressor of notochord reconstitution, as does Hensen's node, when transplanted to other blastoderm isolates. Our results also reveal that the medial edge of the isolate forms a reconstituted primitive streak, which gives rise to the normal derivatives of the definitive primitive streak along its rostrocaudal extent and which expresses typical streak markers. Finally, our results demonstrate that the notochordal inducer also induces the reconstituted Hensen's node and, therefore, acts like a Nieuwkoop Center. These findings increase our understanding of the mechanism of notochord reconstitution, provide new information and a novel model system for studying the induction of the organizer and reveal the potential of the epiblast to regulate its cell fate and patterns of gene expression during late gastrula/early neurula stage in higher vertebrates.

scholarly journals Developmental clock and mechanism of de novo polarization of the mouse embryo

Science ◽  
2020 ◽  
Vol 370 (6522) ◽  
pp. eabd2703
Author(s):  
Meng Zhu ◽  
Jake Cornwall-Scoones ◽  
Peizhe Wang ◽  
Charlotte E. Handford ◽  
Jie Na ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
De Novo ◽  
Cell Fate Specification ◽  
Mouse Development ◽  
Fate Specification ◽  
Apical Domain ◽  
Transcription Factor 4 ◽  
Genome Activation ◽  
Zygotic Genome

Embryo polarization is critical for mouse development; however, neither the regulatory clock nor the molecular trigger that it activates is known. Here, we show that the embryo polarization clock reflects the onset of zygotic genome activation, and we identify three factors required to trigger polarization. Advancing the timing of transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4) expression in the presence of activated Ras homolog family member A (RhoA) induces precocious polarization as well as subsequent cell fate specification and morphogenesis. Tfap2c and Tead4 induce expression of actin regulators that control the recruitment of apical proteins on the membrane, whereas RhoA regulates their lateral mobility, allowing the emergence of the apical domain. Thus, Tfap2c, Tead4, and RhoA are regulators for the onset of polarization and cell fate segregation in the mouse.

scholarly journals Resveratrol Targets Sphingolipid Metabolism to Induce Growth Inhibition in FLT3 ITD Acute Myeloid Leukemia

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 4
Author(s):  
Ersöz ◽  
Adan
Keyword(s):  
Growth Inhibition ◽  
Cell Fate ◽  
De Novo ◽  
Therapeutic Potential ◽  
Annexin V ◽  
Sphingolipid Metabolism ◽  
Ceramide Synthase ◽  
Cytotoxic Effects ◽  
Sphingosine 1 Phosphate ◽  
First Time

Sphingolipids are important signaling lipids which play crucial roles to determine the cell fate. Ceramide, apoptotic central molecule of sphingolipid metabolism, which is produced through de novo pathway by serine palmitoyl transferase (SPT) and can be converted to antiapoptotic sphingosine-1-phosphate (S1P) and glucosyl ceramide (GC) by sphingosine kinase (SK) and glucosyl ceramide synthase (GCS), respectively. It is aimed to investigate therapeutic potential of resveratrol on FLT3-ITD (Internal Tandem Duplication) AML cells and to identify potential mechanism behind resveratrol-mediated growth inhibition by targeting of ceramide metabolism. The cytotoxic effects of resveratrol, SPT inhibitor (myricoin), SK-1 inhibitor (SKI II), GCS inhibitor (PDMP), resveratrol: SPT inhibitor, resveratrol: SK-1 inhibitor and resveratrol: GCS inhibitor combinations on MOLM-13 and MV4-11 FLT3 ITD AML cells were investigated by cell proliferation assay. Apoptosis was evaluated by annexin V/PI double staining. There were synergistic cytotoxic effects of resveratrol with co-administration of SPT inhibitor, SK-1 inhibitor and GCS inhibitor and apoptosis was synergistically induced for resveratrol and its combinations. This preliminary data showed for the first time that resveratrol might inhibit the growth of FLT3 ITD AML cells through targeting ceramide metabolism.

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