scholarly journals The hominoid-specific gene DSCR4 is involved in regulation of human leukocyte migration

2017 ◽  
Author(s):  
Morteza Mahmoudi Saber ◽  
Marziyeh Karimiavargani ◽  
Nilmini Hettiarachchi ◽  
Michiaki Hamada ◽  
Takanori Uzawa ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Immune System ◽  
Neural Crest ◽  
De Novo ◽  
Human Leukocyte ◽  
Neural Crest Cells ◽  
Human Cells ◽  
Specific Gene ◽  
Facial Morphology ◽  
Specific Expression

AbstractDSCR4 (Down syndrome critical region 4) is an orphan retrotransposon-derived de-novo originated protein coding gene present only in hominoids (humans and great apes). Despite being located on the medically critical genomic region and abundance of evidences indicating its functionality, the role of this gene in human cells was utterly unknown. Due to absence of any prior knowledge regarding the function of DSCR4, for the first time here we used a gene-overexpression approach to discover biological importance and cellular roles of this gene. Our analysis strongly indicates DSCR4 to be mainly involved in regulation of the interconnected biological pathways related to cell migration, coagulation and immune system. We also showed that the predicted biological functions are consistent with tissue-specific expression of DSCR4 in migratory immune system leukocyte cells and neural crest cells that shape facial morphology of human embryo. Immune system and neural crest cells are also shown to be affected in Down syndrome patients who suffer from the same type of DSCR4 misregulation as in our study which further support our findings. Providing evidence for the critical roles of DSCR4 in human cells, our findings establish the basis for further investigations on the roles of DSCR4 in etiology of Down syndrome and unique characteristics of hominoids.

Cis-acting regulatory sequences governing Wnt-1 expression in the developing mouse CNS

Development ◽  
1994 ◽  
Vol 120 (8) ◽  
pp. 2213-2224 ◽  
Author(s):  
Y. Echelard ◽  
G. Vassileva ◽  
A.P. McMahon
Keyword(s):  
Neural Crest ◽  
De Novo ◽  
Ectopic Expression ◽  
Neural Crest Cells ◽  
Neural Tube Closure ◽  
Regulatory Sequences ◽  
Lacz Gene ◽  
Mouse Development ◽  
Enhancer Element ◽  
Cis Acting

The protooncogene Wnt-1 encodes a short-range signal which is first expressed in, and appears to demarcate, the presumptive midbrain. Absence of Wnt-1 expression leads to the loss of this region of the brain. By the end of neural tube closure, expression of Wnt-1 extends down much of the dorsal midline of the central nervous system (CNS). Expression is exclusively limited to the CNS at this and later stages. We have investigated the regulation of Wnt-1 during mouse development. Analysis of the embryonic expression of Wnt-1-lacZ reporter constructs spanning nearly 30 kb of the Wnt-1 locus identified a 5.5 kb cis-acting 3′ enhancer element which confers correct temporal and spatial expression on the lacZ gene. Interestingly embryos express Wnt-1-lacZ transgenes in migrating neural crest cells which are derived from the dorsal CNS. Ectopic expression of the Wnt-1-lacZ transgenes may result from perdurance of beta-galactosidase activity in migrating neural crest cells originating from a Wnt-1-expressing region of the dorsal CNS. Alternatively, ectopic expression may arise from transient de novo activation of the transgenes in this cell population. These results are a first step towards addressing how regional cell signaling is established in the mammalian CNS. In addition, transgene expression provides a new tool for the analysis of neural crest development in normal and mutant mouse embryos.

scholarly journals Neural crest cell-cell adhesion controlled by sequential and subpopulation-specific expression of novel cadherins

Development ◽  
1995 ◽  
Vol 121 (5) ◽  
pp. 1321-1332 ◽  
Author(s):  
S. Nakagawa ◽  
M. Takeichi
Keyword(s):  
Neural Crest ◽  
Neural Tube ◽  
Specific Interaction ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Neural Tube Closure ◽  
Beta Catenin ◽  
Intercellular Signaling ◽  
Specific Expression ◽  
Cell Cell

We identified two cadherins, c-cad6B and c-cad7, expressed by neural crest cells at their premigratory and migratory stages, respectively, in chicken embryos. cDNA transfection experiments showed that both were homophilic adhesion molecules, endowing cells with specific adhesiveness. During development, c-cad6B appeared in the neural fold, localizing at the future neural crest area. This expression was maintained during neural tube closure, but disappeared after neural crest cells had left the neural tube, suggesting its role in neural fold fusion and/or in the formation and maintenance of the presumptive neural crest domain in the neural plate/tube. Crest cells emerging from the neural tube lost c-cad6B, and a subpopulation of them began to express c-cad7. This subpopulation-specific expression of c-cad7 persisted during their migration. The migrating c-cad7-positive cells clustered together, and eventually populated restricted regions including the dorsal and ventral roots but very little ganglia. The latter was populated with N-cadherin-positive crest cells. Migrating neural crest cells expressed alpha- and beta-catenin at cell-cell contacts, indicating that their cadherins are functioning. These results suggest that the migrating crest cells are grouped into subpopulations expressing different cadherins. The cadherin-mediated specific interaction between crest cells likely plays a role in intercellular signaling between homotypic cells as well as in sorting of heterotypic cells.

scholarly journals Itpr1 regulates the formation of anterior eye segment tissues derived from neural crest cells

Development ◽  
2021 ◽  
Author(s):  
Akira Kinoshita ◽  
Kaname Ohyama ◽  
Susumu Tanimura ◽  
Katsuya Matsuda ◽  
Tatsuya Kishino ◽  
...  
Keyword(s):  
Neural Crest ◽  
De Novo ◽  
Lymphatic Vessels ◽  
Neural Crest Cells ◽  
Transcriptional Regulators ◽  
Base Pairs ◽  
Nuclear Entry ◽  
Specific Transcript ◽  
Cytoplasmic Membranes ◽  
Anterior Eye Segment

Mutations in ITPR1 cause ataxia and aniridia in individuals with Gillespie syndrome (GLSP). However, the pathogenic mechanisms underlying aniridia remain unclear. We identified a de novo GLSP mutation hotspot in the 3′-region of ITPR1 in five individuals with GLSP. Furthermore, RNA-sequencing and immunoblotting revealed an eye-specific transcript of Itpr1 (218-aa isoform), encoding 218 amino acids (aa). This isoform is localized not only in the endoplasmic reticulum, but also in the nuclear and cytoplasmic membranes. Ocular-specific transcription was repressed by SOX9 and induced by c-MAF in the anterior eye segment (AES) tissues. Mice lacking seven base pairs of the last Itpr1 exon exhibited ataxia and aniridia, in which the iris lymphatic vessels, sphincter and dilator muscles, corneal endothelium and stroma were disrupted, but the neural crest cells persisted after the completion of AES formation. Our analyses revealed that the 218-aa isoform regulated the directionality of actin fibers and the intensity of focal adhesion. The isoform might control the nuclear entry of transcriptional regulators, such as YAP. It is possible that ITPR1 regulates both AES differentiation and muscle contraction in the iris.

scholarly journals Fertility and genomics: comparison of gene expression in contrasting reproductive tissues of female cattle

2016 ◽  
Vol 28 (2) ◽  
pp. 11 ◽  
Author(s):  
P. A. McGettigan ◽  
J. A. Browne ◽  
S. D. Carrington ◽  
M. A. Crowe ◽  
T. Fair ◽  
...  
Keyword(s):  
Gene Expression ◽  
De Novo ◽  
Specific Gene ◽  
Specific Expression ◽  
Tissue Specific ◽  
Information Theoretic ◽  
Variable Expression ◽  
Uterine Endometrium ◽  
Large Numbers ◽  
Female Cattle

To compare gene expression among bovine tissues, large bovine RNA-seq datasets were used, comprising 280 samples from 10 different bovine tissues (uterine endometrium, granulosa cells, theca cells, cervix, embryos, leucocytes, liver, hypothalamus, pituitary, muscle) and generating 260 Gbases of data. Twin approaches were used: an information–theoretic analysis of the existing annotated transcriptome to identify the most tissue-specific genes and a de-novo transcriptome annotation to evaluate general features of the transcription landscape. Expression was detected for 97% of the Ensembl transcriptome with at least one read in one sample and between 28% and 66% at a level of 10 tags per million (TPM) or greater in individual tissues. Over 95% of genes exhibited some level of tissue-specific gene expression. This was mostly due to different levels of expression in different tissues rather than exclusive expression in a single tissue. Less than 1% of annotated genes exhibited a highly restricted tissue-specific expression profile and approximately 2% exhibited classic housekeeping profiles. In conclusion, it is the combined effects of the variable expression of large numbers of genes (73%–93% of the genome) and the specific expression of a small number of genes (<1% of the transcriptome) that contribute to determining the outcome of the function of individual tissues.

scholarly journals Evolutionary Dynamics of the POTE Gene Family in Human and Nonhuman Primates

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 213
Author(s):  
Flavia Angela Maria Maggiolini ◽  
Ludovica Mercuri ◽  
Francesca Antonacci ◽  
Fabio Anaclerio ◽  
Francesco Maria Calabrese ◽  
...  
Keyword(s):  
Gene Family ◽  
Single Molecule ◽  
Copy Number ◽  
Evolutionary Dynamics ◽  
De Novo ◽  
Specific Gene ◽  
Segmental Duplications ◽  
Chromosomal Distribution ◽  
High Sequence Identity ◽  
Specific Expression

POTE (prostate, ovary, testis, and placenta expressed) genes belong to a primate-specific gene family expressed in prostate, ovary, and testis as well as in several cancers including breast, prostate, and lung cancers. Due to their tumor-specific expression, POTEs are potential oncogenes, therapeutic targets, and biomarkers for these malignancies. This gene family maps within human and primate segmental duplications with a copy number ranging from two to 14 in different species. Due to the high sequence identity among the gene copies, specific efforts are needed to assemble these loci in order to correctly define the organization and evolution of the gene family. Using single-molecule, real-time (SMRT) sequencing, in silico analyses, and molecular cytogenetics, we characterized the structure, copy number, and chromosomal distribution of the POTE genes, as well as their expression in normal and disease tissues, and provided a comparative analysis of the POTE organization and gene structure in primate genomes. We were able, for the first time, to de novo sequence and assemble a POTE tandem duplication in marmoset that is misassembled and collapsed in the reference genome, thus revealing the presence of a second POTE copy. Taken together, our findings provide comprehensive insights into the evolutionary dynamics of the primate-specific POTE gene family, involving gene duplications, deletions, and long interspersed nuclear element (LINE) transpositions to explain the actual repertoire of these genes in human and primate genomes.

Regulation of Hoxa2 in cranial neural crest cells involves members of the AP-2 family

Development ◽  
1999 ◽  
Vol 126 (7) ◽  
pp. 1483-1494 ◽  
Author(s):  
M. Maconochie ◽  
R. Krishnamurthy ◽  
S. Nonchev ◽  
P. Meier ◽  
M. Manzanares ◽  
...  
Keyword(s):  
Neural Crest ◽  
Specific Activity ◽  
Family Members ◽  
Neural Crest Cells ◽  
Branchial Arch ◽  
Cranial Neural Crest ◽  
Reporter Expression ◽  
Specific Expression ◽  
Conserved Sequence ◽  
Cranial Neural Crest Cells

Hoxa2 is expressed in cranial neural crest cells that migrate into the second branchial arch and is essential for proper patterning of neural-crest-derived structures in this region. We have used transgenic analysis to begin to address the regulatory mechanisms which underlie neural-crest-specific expression of Hoxa2. By performing a deletion analysis on an enhancer from the Hoxa2 gene that is capable of mediating expression in neural crest cells in a manner similar to the endogenous gene, we demonstrated that multiple cis-acting elements are required for neural-crest-specific activity. One of these elements consists of a sequence that binds to the three transcription factor AP-2 family members. Mutation or deletion of this site in the Hoxa2 enhancer abrogates reporter expression in cranial neural crest cells but not in the hindbrain. In both cell culture co-transfection assays and transgenic embryos AP-2 family members are able to trans-activate reporter expression, showing that this enhancer functions as an AP-2-responsive element in vivo. Reporter expression is not abolished in an AP-2(alpha) null mutant embryos, suggesting redundancy with other AP-2 family members for activation of the Hoxa2 enhancer. Other cis-elements identified in this study critical for neural-crest-specific expression include an element that influences levels of expression and a conserved sequence, which when multimerized directs expression in a broad subset of neural crest cells. These elements work together to co-ordinate and restrict neural crest expression to the second branchial arch and more posterior regions. Our findings have identified the cis-components that allow Hoxa2 to be regulated independently in rhombomeres and cranial neural crest cells.

Induction of melanocyte precursors from neural crest cells surrounding the neural tube-like structures developed in vitro using mouse ES cell culture

2007 ◽  
Vol 27 (1) ◽  
pp. 45-52
Author(s):  
Koh-ichi Atoh ◽  
Manae S. Kurokawa ◽  
Hideshi Yoshikawa ◽  
Chieko Masuda ◽  
Erika Takada ◽  
...  
Keyword(s):  
Cell Culture ◽  
Neural Crest ◽  
Neural Tube ◽  
Neural Crest Cells ◽  
Es Cell ◽  
Mouse Es Cell
Sign in / Sign up

Export Citation Format

Share Document