scholarly journals The complete cell lineage and MAPK- and Otx-dependent specification of the dopaminergic cells in the Ciona brain

Development ◽  
2021 ◽  
Author(s):  
Kouhei Oonuma ◽  
Takehiro G. Kusakabe
Keyword(s):  
Regulatory Networks ◽  
Mapk Pathway ◽  
Cell Lineage ◽  
Dopamine Synthesis ◽  
Dopaminergic Cell ◽  
Dopaminergic Cells ◽  
Daughter Cells ◽  
Bilateral Pair ◽  
Complete Cell ◽  
Fixed Cell

The Ciona larva has served as a unique model for understanding the development of dopaminergic cells at single-cell resolution due to the exceptionally small number of neurons in its brain and its fixed cell lineage during embryogenesis. A recent study suggested that the transcription factors Fer2 and Meis directly regulate the dopamine synthesis genes in Ciona, but the dopaminergic cell lineage and the gene regulatory networks that control the development of dopaminergic cells have not been fully elucidated. Here, we reveal that the dopaminergic cells in Ciona are derived from a bilateral pair of cells called a9.37 cells at the center of the neural plate. The a9.37 cells divide along the anterior-posterior axis, and all of the descendants of the posterior daughter cells differentiate into the dopaminergic cells. We show that the MAPK pathway and the transcription factor Otx are required for the expression of Fer2 in the dopaminergic cell lineage. Our findings establish the cellular and molecular framework for fully understanding the commitment to dopaminergic cells in the simple chordate brain.

The mitosis-regulating and protein-protein interaction activities of Astrin are controlled by Aurora-A-induced phosphorylation

2014 ◽  
Vol 307 (5) ◽  
pp. C466-C478 ◽  
Author(s):  
Shao-Chih Chiu ◽  
Jo-Mei Maureen Chen ◽  
Tong-You Wade Wei ◽  
Tai-Shan Cheng ◽  
Ya-Hui Candice Wang ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Spindle Assembly Checkpoint ◽  
Morphological Changes ◽  
Spindle Assembly ◽  
Aurora A ◽  
Protein Protein Interaction ◽  
Daughter Cells ◽  
Sister Chromatids ◽  
Complicated Process ◽  
Spindle Stability

Cells display dramatic morphological changes in mitosis, where numerous factors form regulatory networks to orchestrate the complicated process, resulting in extreme fidelity of the segregation of duplicated chromosomes into two daughter cells. Astrin regulates several aspects of mitosis, such as maintaining the cohesion of sister chromatids by inactivating Separase and stabilizing spindle, aligning and segregating chromosomes, and silencing spindle assembly checkpoint by interacting with Src kinase-associated phosphoprotein (SKAP) and cytoplasmic linker-associated protein-1α (CLASP-1α). To understand how Astrin is regulated in mitosis, we report here that Astrin acts as a mitotic phosphoprotein, and Aurora-A phosphorylates Astrin at Ser115. The phosphorylation-deficient mutant Astrin S115A abnormally activates spindle assembly checkpoint and delays mitosis progression, decreases spindle stability, and induces chromosome misalignment. Mechanistic analyses reveal that Astrin phosphorylation mimicking mutant S115D, instead of S115A, binds and induces ubiquitination and degradation of securin, which sequentially activates Separase, an enzyme required for the separation of sister chromatids. Moreover, S115A fails to bind mitosis regulators, including SKAP and CLASP-1α, which results in the mitotic defects observed in Astrin S115A-transfected cells. In conclusion, Aurora-A phosphorylates Astrin and guides the binding of Astrin to its cellular partners, which ensures proper progression of mitosis.

scholarly journals Activating mutations in BRAF disrupt the hypothalamo-pituitary axis leading to hypopituitarism in mice and humans

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Angelica Gualtieri ◽  
Nikolina Kyprianou ◽  
Louise C. Gregory ◽  
Maria Lillina Vignola ◽  
James G. Nicholson ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Critical Role ◽  
Cell Lineage ◽  
Activating Mutations ◽  
Pathway Activation ◽  
Tumour Formation ◽  
Conditional Expression ◽  
Cell Cycle Inhibitors ◽  
Mutation Braf

AbstractGermline mutations in BRAF and other components of the MAPK pathway are associated with the congenital syndromes collectively known as RASopathies. Here, we report the association of Septo-Optic Dysplasia (SOD) including hypopituitarism and Cardio-Facio-Cutaneous (CFC) syndrome in patients harbouring mutations in BRAF. Phosphoproteomic analyses demonstrate that these genetic variants are gain-of-function mutations leading to activation of the MAPK pathway. Activation of the MAPK pathway by conditional expression of the BrafV600E/+ allele, or the knock-in BrafQ241R/+ allele (corresponding to the most frequent human CFC-causing mutation, BRAF p.Q257R), leads to abnormal cell lineage determination and terminal differentiation of hormone-producing cells, causing hypopituitarism. Expression of the BrafV600E/+ allele in embryonic pituitary progenitors leads to an increased expression of cell cycle inhibitors, cell growth arrest and apoptosis, but not tumour formation. Our findings show a critical role of BRAF in hypothalamo-pituitary-axis development both in mouse and human and implicate mutations found in RASopathies as a cause of endocrine deficiencies in humans.

scholarly journals From blastocyst to gastrula: gene regulatory networks of embryonic stem cells and early mouse embryogenesis

2014 ◽  
Vol 369 (1657) ◽  
pp. 20130542 ◽  
Author(s):  
David-Emlyn Parfitt ◽  
Michael M. Shen
Keyword(s):  
Stem Cells ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Network Models ◽  
Cell Types ◽  
Mammalian Development ◽  
A Genome

To date, many regulatory genes and signalling events coordinating mammalian development from blastocyst to gastrulation stages have been identified by mutational analyses and reverse-genetic approaches, typically on a gene-by-gene basis. More recent studies have applied bioinformatic approaches to generate regulatory network models of gene interactions on a genome-wide scale. Such models have provided insights into the gene networks regulating pluripotency in embryonic and epiblast stem cells, as well as cell-lineage determination in vivo . Here, we review how regulatory networks constructed for different stem cell types relate to corresponding networks in vivo and provide insights into understanding the molecular regulation of the blastocyst–gastrula transition.

scholarly journals 78 NONINVASIVE CELL LINEAGE TRACING IN BOVINE EMBRYOS FROM 2-CELL STAGE UP TO BLASTOCYST STAGE

2015 ◽  
Vol 27 (1) ◽  
pp. 132
Author(s):  
L. P. Sepulveda-Rincon ◽  
D. Dube ◽  
P. Adenot ◽  
L. Laffont ◽  
S. Ruffini ◽  
...  
Keyword(s):  
Cell Mass ◽  
Cell Lineage ◽  
Blastocyst Stage ◽  
Lineage Tracing ◽  
Specific Cell ◽  
Bovine Embryos ◽  
Cell Stage ◽  
Daughter Cells ◽  
Significant Difference ◽  
Allocation Patterns

The first lineage specification occurs during pre-implantation mammalian development. At the blastocyst stage, 2 cell lineages can be distinguished: the inner cell mass (ICM) and the trophectoderm (TE). The exact timing when embryo cells are skewed to these lineages is not clearly determined in mammalian species. In murine embryos, it has been suggested that the first cleavage plane might be related to the embryonic-abembryonic (Em-Ab) axis at blastocyst stage. Thus, the daughter cells of the 2-cell embryo might already be predisposed to a specific cell lineage further on development. The objective of the present study was to observe how the first cleavage in bovine embryos may be related to cell lineage allocation at the blastocyst stage, using a noninvasive tracing approach. Bovine oocytes were harvested, in vitro matured, and fertilised. At the 2-cell stage, embryos were injected in one blastomere with the membrane tracer DiI. At the blastocyst stage, embryos (n = 346) were classified as orthogonal when the Em-Ab axis was orthogonally divided by the borderline between labelled and non-labelled cells; as deviant if the borderline was overlapping the Em-Ab axis; and as random when the labelled and non-labelled cells were randomly distributed. Total cell count (TCC) and the ICM/TE ratio was allowed by DNA staining with 4′,6-diamidino-2-phenylindole (DAPI) and by immunostaining of the ICM with Sox2 antibody. Analysis of variance was performed by one-way ANOVA employing IBM SPSS v21 (SPSS Inc., Chicago, IL, USA) to determine any difference between the cell lineage allocation patterns, TCC, and the ICM/TE ratio. P-values = 0.05 were considered significant. All values are reported as mean ± standard error of mean. Within 40 repetitions, the blastocyst classification was as follows: orthogonal 14.9% (±2.32, n = 56), deviant 22.2% (±2.58, n = 80), and random 62.9% (±2.64, n = 210). A significant difference was found in the incidence between the random group against the orthogonal and deviant, but not between the latter two. Regarding TCC, a significant difference was observed only between the orthogonal (99.6 ± 11.7 cells, n = 15) and deviant (135 ± 7.3 cells, n = 25) groups, but not with random embryos (116 ± 5.5 cells, n = 42). Finally, no significant difference was found among the groups concerning the ICM/TE ratio (0.43 ± 0.07 for orthogonal, n = 7; 0.54 ± 0.06 for deviant, n = 14; and 0.40 ± 0.03 for random embryos, n = 26). In conclusion, bovine embryos present a marked tendency for a random distribution of the daughter cells derived from the 2-cell blastomeres. However, around 37% of the blastocysts present a patterned cell division, where the daughter cells remain together through pre-implantation development. The effect of these cell lineage allocation patterns on implantation and further embryo development needs to be addressed.The authors acknowledge Laboratoire d'Excellence Revive (Investissement d'Avenir, ANR-10-LABX-73) and CONACyT Mexico for funding.

Features of cell lineage in preimplantation mouse development

Development ◽  
1978 ◽  
Vol 48 (1) ◽  
pp. 53-72
Author(s):  
C. F. Graham ◽  
Z. A. Deussen
Keyword(s):  
Inner Cell Mass ◽  
Cell Mass ◽  
Cell Lineage ◽  
The Other ◽  
Mouse Development ◽  
Cell Stage ◽  
Daughter Cells ◽  
Preimplantation Mouse ◽  
Peripheral Cells

The cell lineage of the mouse was studied from the 2-cell stage to the blastocyst. Lineage to the 8-cell stage was followed under the microscope. Each cell from the 2-cell stage divided to form two daughter cells which remained attached. Subsequently, these two daughters each produced two descendants; one of these descendants regularly lay deep in the structure of the embryo while the other was peripheral. Lineage to the blastocyst was followed by injecting oil drops into cells at the 8-cell stage, and then following the segregation of these drops into the inner cell mass and trophectoderm. Between the 8-cell stage and the blastocyst, the deep cells contributed more frequently to the inner cell mass than did the peripheral cells.

scholarly journals Light-sheet fluorescence imaging charts the gastrula origin of vascular endothelial cells in early zebrafish embryos

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Meijun Pang ◽  
Linlu Bai ◽  
Weijian Zong ◽  
Xu Wang ◽  
Ye Bu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Fluorescence Imaging ◽  
Vascular Endothelial Cells ◽  
Cell Lineage ◽  
Light Sheet ◽  
Model Organisms ◽  
Vascular Endothelial ◽  
Anterior Trunk ◽  
Potential Applications ◽  
Complete Cell

Abstract It remains challenging to construct a complete cell lineage map of the origin of vascular endothelial cells in any vertebrate embryo. Here, we report the application of in toto light-sheet fluorescence imaging of embryos to trace the origin of vascular endothelial cells (ECs) at single-cell resolution in zebrafish. We first adapted a previously reported method to embryo mounting and light-sheet imaging, created an alignment, fusion, and extraction all-in-one software (AFEIO) for processing big data, and performed quantitative analysis of cell lineage relationships using commercially available Imaris software. Our data revealed that vascular ECs originated from broad regions of the gastrula along the dorsal–ventral and anterior–posterior axes, of which the dorsal–anterior cells contributed to cerebral ECs, the dorsal–lateral cells to anterior trunk ECs, and the ventral–lateral cells to posterior trunk and tail ECs. Therefore, this work, to our knowledge, charts the first comprehensive map of the gastrula origin of vascular ECs in zebrafish, and has potential applications for studying the origin of any embryonic organs in zebrafish and other model organisms.

scholarly journals The Influence of the MAPK Pathway on T Cell Lineage Commitment

Immunity ◽  
1997 ◽  
Vol 7 (5) ◽  
pp. 609-618 ◽  
Author(s):  
Leslie L Sharp ◽  
David A Schwarz ◽  
Cynthia M Bott ◽  
Christopher J Marshall ◽  
Stephen M Hedrick
Keyword(s):  
T Cell ◽  
Mapk Pathway ◽  
Cell Lineage ◽  
Lineage Commitment

Extensions of the bifurcating autoregressive model for cell lineage studies

1999 ◽  
Vol 36 (04) ◽  
pp. 1225-1233 ◽  
Author(s):  
R. M. Huggins ◽  
I. V. Basawa
Keyword(s):  
Environmental Effects ◽  
Autoregressive Model ◽  
Cell Lineage ◽  
Data Sets ◽  
Daughter Cells ◽  
Mother And Daughter ◽  
Model Cell ◽  
Lines Of Descent ◽  
Lineage Trees ◽  
Sister Cells

The bifurcating autoregressive model has been used previously to model cell lineage data. A feature of this model is that each line of descendants from an initial cell follows an AR(1) model, and that the environmental effects on sisters are correlated. However, this model concentrates on modelling the correlations between mother and daughter cells and between sister cells, and does not explain the large correlations between more distant relatives observed by some authors. Here the model is extended, firstly by allowing lines of descent to follow an ARMA(p,q) model rather than an AR(1) model, and secondly by allowing correlations between the environmental effects of relatives more distant than sisters. The models are applied to several data sets consisting of independent cell lineage trees.

scholarly journals Light-Sheet Fluorescence Imaging Charts the Gastrula Origin of Vascular Endothelial Cells in Early Zebrafish Embryos

2020 ◽  
Author(s):  
Meijun Pang ◽  
Linlu Bai ◽  
Weijian Zong ◽  
Xu Wang ◽  
Ye Bu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Fluorescence Imaging ◽  
Vascular Endothelial Cells ◽  
Cell Lineage ◽  
Light Sheet ◽  
Model Organisms ◽  
Vascular Endothelial ◽  
Anterior Trunk ◽  
Potential Applications ◽  
Complete Cell

AbstractIt remains challenging to construct a complete cell lineage map of the origin of vascular endothelial cells in any vertebrate embryo. Here, we report the application of in toto light-sheet fluorescence imaging of embryos to tracing the origin of vascular endothelial cells (ECs) at single-cell resolution in zebrafish. We first adapted a previously-reported method to mount embryos and light-sheet imaging, created an alignment, fusion, and extraction all-in-one software (AFEIO) for processing big data, and performed quantitative analysis of cell lineage relationships using commercially-available Imaris software. Our data revealed that vascular ECs originated from broad regions of the gastrula along the dorsal-ventral and anterior-posterior axes, of which the dorsal-anterior cells contributed to cerebral ECs, the dorsal-lateral cells to anterior trunk ECs, and the ventral-lateral cells to posterior trunk and tail ECs. Therefore, this work, to our knowledge, charts the first comprehensive map of the gastrula origin of vascular ECs in zebrafish, and has potential applications for studying the origin of any embryonic organs in zebrafish and other model organisms.

scholarly journals Enhanced TF binding site maps improve regulatory networks learned from accessible chromatin data

2019 ◽  
Author(s):  
Shubhada R. Kulkarni ◽  
D. Marc Jones ◽  
Klaas Vandepoele
Keyword(s):  
Binding Site ◽  
Dna Sequences ◽  
Regulatory Networks ◽  
Transcriptional Control ◽  
Chromatin Accessibility ◽  
Systematic Evaluation ◽  
Open Chromatin ◽  
Ensemble Approach ◽  
Complete Cell ◽  
Regulatory Dna

ABSTRACTDetermining where transcription factors (TF) bind in genomes provides insights into which transcriptional programs are active across organs, tissue types, and environmental conditions. Recent advances in high-throughput profiling of regulatory DNA have yielded large amounts of information about chromatin accessibility. Interpreting the functional significance of these datasets requires knowledge of which regulators are likely to bind these regions. This can be achieved by using information about TF binding preferences, or motifs, to identify TF binding events that are likely to be functional. Although different approaches exist to map motifs to DNA sequences, a systematic evaluation of these tools in plants is missing. Here we compare four motif mapping tools widely used in the Arabidopsis research community and evaluate their performance using chromatin immunoprecipitation datasets for 40 TFs. Downstream gene regulatory network (GRN) reconstruction was found to be sensitive to the motif mapper used. We further show that the low recall of FIMO, one of the most frequently used motif mapping tools, can be overcome by using an Ensemble approach, which combines results from different mapping tools. Several examples are provided demonstrating how the Ensemble approach extends our view on transcriptional control for TFs active in different biological processes. Finally, a new protocol is presented to efficiently derive more complete cell type-specific GRNs through the integrative analysis of open chromatin regions, known binding site information, and expression datasets.

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