scholarly journals A 37 kb region upstream of Brachyury comprising a notochord enhancer is essential for notochord and tail development

Development ◽  
2021 ◽  
Author(s):  
Dennis Schifferl ◽  
Manuela Scholze-Wittler ◽  
Lars Wittler ◽  
Jesse V. Veenvliet ◽  
Frederic Koch ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Mouse Embryos ◽  
Border Region ◽  
Specific Expression ◽  
T Box ◽  
Tail Development ◽  
Notochord Cell ◽  
Organizing Center ◽  
Cell Type Specific Expression ◽  
And Function

The node-streak border region comprising notochord progenitor cells (NPCs) at the posterior node and neuro-mesodermal progenitor cells (NMPs) in the adjacent epiblast is the prime organizing center for axial elongation in mouse embryos. The T-box transcription factor Brachyury (T) is essential for both, formation of the notochord and maintenance of NMPs, and thus is a key regulator of trunk and tail development. The T promoter controlling T expression in NMPs and nascent mesoderm has been characterized in detail. However, control elements for T expression in the notochord have not been identified yet. We have generated a series of deletion alleles by CRISPR/Cas9 genome editing in mESCs, and analyzed their effects in mutant mouse embryos. We identified a 37 kb region upstream of T essential for notochord function and tailbud outgrowth. Within that region we discovered a T binding enhancer required for notochord cell specification and differentiation. Our data reveal a complex regulatory landscape controlling cell type-specific expression and function of T in NMP/nascent mesoderm and node/notochord allowing proper trunk and tail development.

scholarly journals Function of Circular RNAs in Fish and Their Potential Application as Biomarkers

2021 ◽  
Vol 22 (13) ◽  
pp. 7119
Author(s):  
Golam Rbbani ◽  
Artem Nedoluzhko ◽  
Jorge Galindo-Villegas ◽  
Jorge M. O. Fernandes
Keyword(s):  
Growth Regulation ◽  
Functional Characterization ◽  
Circular Rnas ◽  
Farmed Fish ◽  
Developmentally Regulated ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Taxonomic Groups ◽  
And Function

Circular RNAs (circRNAs) are an emerging class of regulatory RNAs with a covalently closed-loop structure formed during pre-mRNA splicing. Recent advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of novel approaches to their identification and functional characterization. CircRNAs are stable, developmentally regulated, and show tissue- and cell-type-specific expression across different taxonomic groups. They play a crucial role in regulating various biological processes at post-transcriptional and translational levels. However, the involvement of circRNAs in fish immunity has only recently been recognized. There is also broad evidence in mammals that the timely expression of circRNAs in muscle plays an essential role in growth regulation but our understanding of their expression and function in teleosts is still very limited. Here, we discuss the available knowledge about circRNAs and their role in growth and immunity in vertebrates from a comparative perspective, with emphasis on cultured teleost fish. We expect that the interest in teleost circRNAs will increase substantially soon, and we propose that they may be used as biomarkers for selective breeding of farmed fish, thus contributing to the sustainability of the aquaculture sector.

scholarly journals Cell-specific expression and individual function of prohormone convertase PC1/3 in Tribolium larval growth highlights major evolutionary changes between beetle and fly neuroendocrine systems

EvoDevo ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sonja Fritzsche ◽  
Vera S. Hunnekuhl
Keyword(s):  
Larval Growth ◽  
Neuroendocrine System ◽  
Small Subset ◽  
Specific Cell ◽  
Specific Expression ◽  
Individual Function ◽  
Evolutionary Changes ◽  
Cell Groups ◽  
Cell Type Specific Expression ◽  
And Function

Abstract Background The insect neuroendocrine system acts in the regulation of physiology, development and growth. Molecular evolution of this system hence has the potential to allow for major biological differences between insect groups. Two prohormone convertases, PC1/3 and PC2, are found in animals and both function in the processing of neuropeptide precursors in the vertebrate neurosecretory pathway. Whereas PC2-function is conserved between the fly Drosophila and vertebrates, ancestral PC1/3 was lost in the fly lineage and has not been functionally studied in any protostome. Results In order to understand its original functions and the changes accompanying the gene loss in the fly, we investigated PC1/3 and PC2 expression and function in the beetle Tribolium castaneum. We found that PC2 is broadly expressed in the nervous system, whereas surprisingly, PC1/3 expression is restricted to specific cell groups in the posterior brain and suboesophageal ganglion. Both proteases have parallel but non-redundant functions in adult beetles’ viability and fertility. Female infertility following RNAi is caused by a failure to deposit sufficient yolk to the developing oocytes. Larval RNAi against PC2 produced moulting defects where the larvae were not able to shed their old cuticle. This ecdysis phenotype was also observed in a small subset of PC1/3 knockdown larvae and was strongest in a double knockdown. Unexpectedly, most PC1/3-RNAi larvae showed strongly reduced growth, but went through larval moults despite minimal to zero weight gain. Conclusions The cell type-specific expression of PC1/3 and its essential requirement for larval growth highlight the important role of this gene within the insect neuroendocrine system. Genomic conservation in most insect groups suggests that it has a comparable individual function in other insects as well, which has been replaced by alternative mechanisms in flies.

scholarly journals Adeno-Associated Virus Technologies and Methods for Targeted Neuronal Manipulation

2019 ◽  
Author(s):  
Leila Haery ◽  
Benjamin E. Deverman ◽  
Katherine Matho ◽  
Ali Cetin ◽  
Kenton Woodard ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Cell Types ◽  
Regulatory Elements ◽  
Specific Cell ◽  
Specific Expression ◽  
Adeno Associated Virus ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
And Function ◽  
Novel Applications

AbstractCell-type-specific expression of molecular tools and sensors is critical to construct circuit diagrams and to investigate the activity and function of neurons within the nervous system. Strategies for targeted manipulation include combinations of classical genetic tools such as Cre/loxP and Flp/FRT, use of cis-regulatory elements, targeted knock-in transgenic mice, and gene delivery by AAV and other viral vectors. The combination of these complex technologies with the goal of precise neuronal targeting is a challenge in the lab. This report will discuss the theoretical and practical aspects of combining current technologies and establish best practices for achieving targeted manipulation of specific cell types. Novel applications and tools, as well as areas for development, will be envisioned and discussed.

scholarly journals Systems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis

2019 ◽  
Vol 21 (1) ◽  
pp. 132 ◽  
Author(s):  
Hironori Matsuyama ◽  
Hiroshi I. Suzuki
Keyword(s):  
Expression Patterns ◽  
System Level ◽  
Mirna Biogenesis ◽  
Mirna Regulation ◽  
Specific Expression ◽  
Synthetic Gene Circuits ◽  
Mirna Genes ◽  
Super Enhancer ◽  
Cell Type Specific Expression ◽  
And Function

MicroRNAs (miRNAs) are approximately 22-nucleotide-long, small non-coding RNAs that post-transcriptionally regulate gene expression. The biogenesis of miRNAs involves multiple steps, including the transcription of primary miRNAs (pri-miRNAs), nuclear Drosha-mediated processing, cytoplasmic Dicer-mediated processing, and loading onto Argonaute (Ago) proteins. Further, miRNAs control diverse biological and pathological processes via the silencing of target mRNAs. This review summarizes recent findings regarding the quantitative aspects of miRNA homeostasis, including Drosha-mediated pri-miRNA processing, Ago-mediated asymmetric miRNA strand selection, and modifications of miRNA pathway components, as well as the roles of RNA modifications (epitranscriptomics), epigenetics, transcription factor circuits, and super-enhancers in miRNA regulation. These recent advances have facilitated a system-level understanding of miRNA networks, as well as the improvement of RNAi performance for both gene-specific targeting and genome-wide screening. The comprehensive understanding and modeling of miRNA biogenesis and function have been applied to the design of synthetic gene circuits. In addition, the relationships between miRNA genes and super-enhancers provide the molecular basis for the highly biased cell type-specific expression patterns of miRNAs and the evolution of miRNA–target connections, while highlighting the importance of alterations of super-enhancer-associated miRNAs in a variety of human diseases.

scholarly journals Cell Type-specific Expression of the Mas Proto-oncogene in Testis

2002 ◽  
Vol 50 (5) ◽  
pp. 691-695 ◽  
Author(s):  
Natalia Alenina ◽  
Tatjana Baranova ◽  
Eugene Smirnow ◽  
Michael Bader ◽  
Andrea Lippoldt ◽  
...  
Keyword(s):  
Leydig Cells ◽  
Rnase Protection Assay ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Specific Expression ◽  
Rnase Protection ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
And Function ◽  
Old Mice

The Mas proto-oncogene encodes a G-protein-coupled receptor with the common seven transmembrane domains and may be involved in the actions of angiotensins. Because Mas is highly expressed in testis, we investigated the cell type-specificity and the onset of expression of the gene in this organ. Using an RNase protection assay, it could be shown that neither whole testes nor cultured Sertoli and Leydig cells of 12-day-old mice express Mas mRNA. Mas expression is first detected in 18-day-old mice and thereafter increases continuously until 6 months of age. By in situ hybridization, the expression could be localized to Leydig cells and Sertoli cells, the signals being much more pronounced in the former. A weak signal was detected in primary spermatocytes. The strong ontogenetically controlled and cell type-specific expression of this membrane-bound receptor in testis implicates a role for the Mas proto-oncogene in testis maturation and function.

Cell type-specific expression of the mouse peripherin gene requires both upstream and intragenic sequences in transgenic mouse embryos

1996 ◽  
Vol 92 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Laurence Leconte ◽  
Miklos Santha ◽  
Cécile Fort ◽  
Chatal Poujeol ◽  
Marie-Madeleine Portier ◽  
...  
Keyword(s):  
Transgenic Mouse ◽  
Mouse Embryos ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

scholarly journals GATA3 up-regulation associated with surface expression of CD294/CRTH2: a unique feature of human Th cells

Blood ◽  
2007 ◽  
Vol 109 (10) ◽  
pp. 4343-4350 ◽  
Author(s):  
Umberto De Fanis ◽  
Francesca Mori ◽  
Rebecca J. Kurnat ◽  
Won Kyung Lee ◽  
Maria Bova ◽  
...  
Keyword(s):  
Cell Function ◽  
Surface Expression ◽  
Th2 Cells ◽  
Specific Expression ◽  
Th Cells ◽  
T Box ◽  
Th Cell ◽  
Ifn Γ ◽  
Additional Level ◽  
And Function

Abstract GATA-3 and T-box expressed in T cells (T-bet) play central roles in Th-cell development and function. Consistently, studies in mice document their selective expression in Th1 and Th2 cells, respectively. In contrast, it is not clear whether these genes are regulated in human Th cells. Here we show that T-bet expression is polarized to a comparable degree in human and mouse Th-cell cultures, while only mouse GATA3 is subject to substantial regulation. This did not reflect differential skewing efficiency in human versus mouse cultures, as these contained similar frequencies of IFN-γ– and IL-4–producing cells. However, GATA-3 was expressed at significantly higher levels in human IL-4–producing cells enriched via capture with monoclonal antibodies (mAbs) against the PGD2 receptor, CRTH2, the best selective Th2-cell surface marker to date. Along with increased IL-4 and GATA-3, CRTH2+ Th cells isolated from Th2-skewed cultures or the circulating memory pool exhibited markedly decreased IFN-γ and T-bet expression. Thus, the human GATA-3 gene is not regulated in response to polarizing signals that are sufficient to direct Th2-specific expression in mouse cells. This postulates the involvement of an additional level of complexity in the regulation of human GATA-3 expression and stresses the existence of nontrivial differences in the regulation of human versus mouse T-cell function.

scholarly journals The versatility of liver X receptors in T cell homeostasis: Location, location, location!

2021 ◽  
Vol 218 (4) ◽  
Author(s):  
Truong San Phan ◽  
Thomas Brunner
Keyword(s):  
T Cell ◽  
Nuclear Receptors ◽  
Target Cells ◽  
Liver X Receptors ◽  
T Cell Homeostasis ◽  
Specific Expression ◽  
Cell Homeostasis ◽  
Cell Type Specific Expression ◽  
X Receptors ◽  
And Function

Nuclear receptors control the transcriptional program of target cells and thereby their phenotype and activities. Two complementary studies by Micheals et al. (https://doi.org/10.1084/jem.20201311) and Chan et al. (https://doi.org/10.1084/jem.20200318) published in JEM uncover the cell type–specific expression and role of the nuclear receptors liver X receptors in the regulation of T cell homeostasis and function.

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