scholarly journals i-8. Four Developmental Defects associated with Cavum Septi Pellucidi

1968 ◽  
Vol 10 ◽  
pp. 178b-179
Author(s):  
Tetsuya Leslie SASABE ◽  
Katsuhito AKAGI ◽  
Yoshikazu IWATA ◽  
Masatsugi KOBATAKE ◽  
Fujio UEMURA
Keyword(s):  
Cavum Septi Pellucidi ◽  
Developmental Defects

scholarly journals Molecular regulation of Snai2 in development and disease

2019 ◽  
Vol 132 (23) ◽  
Author(s):  
Wenhui Zhou ◽  
Kayla M. Gross ◽  
Charlotte Kuperwasser
Keyword(s):  
Transcription Factor ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Zinc Finger Protein ◽  
Main Role ◽  
Biological Processes ◽  
Developmental Defects ◽  
Mesenchymal Transition ◽  
Damage Repair

ABSTRACT The transcription factor Snai2, encoded by the SNAI2 gene, is an evolutionarily conserved C2H2 zinc finger protein that orchestrates biological processes critical to tissue development and tumorigenesis. Initially characterized as a prototypical epithelial-to-mesenchymal transition (EMT) transcription factor, Snai2 has been shown more recently to participate in a wider variety of biological processes, including tumor metastasis, stem and/or progenitor cell biology, cellular differentiation, vascular remodeling and DNA damage repair. The main role of Snai2 in controlling such processes involves facilitating the epigenetic regulation of transcriptional programs, and, as such, its dysregulation manifests in developmental defects, disruption of tissue homeostasis, and other disease conditions. Here, we discuss our current understanding of the molecular mechanisms regulating Snai2 expression, abundance and activity. In addition, we outline how these mechanisms contribute to disease phenotypes or how they may impact rational therapeutic targeting of Snai2 dysregulation in human disease.

scholarly journals Early-Life Exposure to Environmental Contaminants Perturbs the Sperm Epigenome and Induces Negative Pregnancy Outcomes for Three Generations via the Paternal Lineage

Epigenomes ◽  
2021 ◽  
Vol 5 (2) ◽  
pp. 10
Author(s):  
Clotilde Maurice ◽  
Mathieu Dalvai ◽  
Romain Lambrot ◽  
Astrid Deschênes ◽  
Marie-Pier Scott-Boyer ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Pregnancy Outcomes ◽  
Sperm Quality ◽  
The Arctic ◽  
Congenital Defects ◽  
Developmental Defects ◽  
Early Life Exposure ◽  
Sperm Dna ◽  
Inuit Population ◽  
Sperm Dna Methylation

Due to the grasshopper effect, the Arctic food chain in Canada is contaminated with persistent organic pollutants (POPs) of industrial origin, including polychlorinated biphenyls and organochlorine pesticides. Exposure to POPs may be a contributor to the greater incidence of poor fetal growth, placental abnormalities, stillbirths, congenital defects and shortened lifespan in the Inuit population compared to non-Aboriginal Canadians. Although maternal exposure to POPs is well established to harm pregnancy outcomes, paternal transmission of the effects of POPs is a possibility that has not been well investigated. We used a rat model to test the hypothesis that exposure to POPs during gestation and suckling leads to developmental defects that are transmitted to subsequent generations via the male lineage. Indeed, developmental exposure to an environmentally relevant Arctic POPs mixture impaired sperm quality and pregnancy outcomes across two subsequent, unexposed generations and altered sperm DNA methylation, some of which are also observed for two additional generations. Genes corresponding to the altered sperm methylome correspond to health problems encountered in the Inuit population. These findings demonstrate that the paternal methylome is sensitive to the environment and that some perturbations persist for at least two subsequent generations. In conclusion, although many factors influence health, paternal exposure to contaminants plays a heretofore-underappreciated role with sperm DNA methylation contributing to the molecular underpinnings involved.

scholarly journals Molecular and Functional Mapping of the Piebald Deletion Complex on Mouse Chromosome 14

Genetics ◽  
2001 ◽  
Vol 157 (2) ◽  
pp. 803-815
Author(s):  
Jeffrey J Roix ◽  
Aaron Hagge-Greenberg ◽  
Dennis M Bissonnette ◽  
Sandra Rodick ◽  
Liane B Russell ◽  
...  
Keyword(s):  
Mouse Chromosome ◽  
System Development ◽  
Genomic Region ◽  
Nervous System Development ◽  
Chromosome 14 ◽  
Developmental Defects ◽  
Oak Ridge ◽  
Recessive Mutations ◽  
Large Deletions ◽  
Critical Regions

Abstract The piebald deletion complex is a set of overlapping chromosomal deficiencies surrounding the endothelin receptor B locus collected during the Oak Ridge specific-locus-test mutagenesis screen. These chromosomal deletions represent an important resource for genetic studies to dissect the functional content of a genomic region, and several developmental defects have been associated with mice homozygous for distinct piebald deletion alleles. We have used molecular markers to order the breakpoints for 20 deletion alleles that span a 15.7–18-cM region of distal mouse chromosome 14. Large deletions covering as much as 11 cM have been identified that will be useful for regionally directed mutagenesis screens to reveal recessive mutations that disrupt development. Deletions identified as having breakpoints positioned within previously described critical regions have been used in complementation studies to further define the functional intervals associated with the developmental defects. This has focused our efforts to isolate genes required for newborn respiration and survival, skeletal patterning and morphogenesis, and central nervous system development.

scholarly journals mRNA Surveillance Complex PELOTA-HBS1 Regulates Phosphoinositide-Dependent Protein Kinase1 and Plant Growth

2021 ◽  
Author(s):  
Wei Kong ◽  
Shutang Tan ◽  
Qing Zhao ◽  
De-Li Lin ◽  
Zhi-Hong Xu ◽  
...  
Keyword(s):  
Quality Control ◽  
Messenger Rna ◽  
Loss Of Function ◽  
Yeast Saccharomyces Cerevisiae ◽  
Developmental Defects ◽  
Mrna Surveillance ◽  
Dna Insertion ◽  
Dependent Protein ◽  
Heterodimeric Complex ◽  
Severe Growth

Abstract The quality control system for messenger RNA (mRNA) is fundamental for cellular activities in eukaryotes. To elucidate the molecular mechanism of 3’-Phosphoinositide-Dependent Protein Kinase1 (PDK1), a master regulator that is essential throughout eukaryotic growth and development, we employed a forward genetic approach to screen for suppressors of the loss-of-function T-DNA insertion double mutant pdk1.1 pdk1.2 in Arabidopsis thaliana. Notably, the severe growth attenuation of pdk1.1 pdk1.2 was rescued by sop21 (suppressor of pdk1.1 pdk1.2), which harbours a loss-of-function mutation in PELOTA1 (PEL1). PEL1 is a homologue of mammalian PELOTA and yeast (Saccharomyces cerevisiae) DOM34p, which each form a heterodimeric complex with the GTPase HBS1 (HSP70 SUBFAMILY B SUPPRESSOR1, also called SUPERKILLER PROTEIN7, SKI7), a protein that is responsible for ribosomal rescue and thereby assures the quality and fidelity of mRNA molecules during translation. Genetic analysis further revealed that a dysfunctional PEL1-HBS1 complex failed to degrade the T-DNA-disrupted PDK1 transcripts, which were truncated but functional, and thus rescued the growth and developmental defects of pdk1.1 pdk1.2. Our studies demonstrated the functionality of a homologous PELOTA-HBS1 complex and identified its essential regulatory role in plants, providing insights into the mechanism of mRNA quality control.

scholarly journals Preliminary Results Regarding Sleep in a Zebrafish Model of Autism Spectrum Disorder

2021 ◽  
Vol 11 (5) ◽  
pp. 556
Author(s):  
Madalina Andreea Robea ◽  
Alin Ciobica ◽  
Alexandrina-Stefania Curpan ◽  
Gabriel Plavan ◽  
Stefan Strungaru ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Valproic Acid ◽  
Social Behavior ◽  
Antiepileptic Drug ◽  
Alternative Model ◽  
Neurological Diseases ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Zebrafish Model ◽  
Developmental Defects

Autism spectrum disorder (ASD) is one of the most salient developmental neurological diseases and remarkable similarities have been found between humans and model animals of ASD. A common method of inducing ASD in zebrafish is by administrating valproic acid (VPA), which is an antiepileptic drug that is strongly linked with developmental defects in children. In the present study we replicated and extended the findings of VPA on social behavior in zebrafish by adding several sleep observations. Juvenile zebrafish manifested hyperactivity and an increase in ASD-like social behaviors but, interestingly, only exhibited minimal alterations in sleep. Our study confirmed that VPA can generate specific ASD symptoms, indicating that the zebrafish is an alternative model in this field of research.

scholarly journals Restriction of cytosolic sucrose hydrolysis profoundly alters development, metabolism and gene expression in Arabidopsis roots

2020 ◽  
Author(s):  
Cristina Pignocchi ◽  
Alexander Ivakov ◽  
Regina Feil ◽  
Martin Trick ◽  
Marilyn Pike ◽  
...  
Keyword(s):  
Growth And Development ◽  
Low Carbon ◽  
Sucrose Hydrolysis ◽  
Developmental Defects ◽  
Altered Expression ◽  
Signalling Molecules ◽  
Exogenous Glucose ◽  
Rich Information ◽  
Sugar Levels ◽  
Reduced Activity

Abstract Plant roots depend on sucrose imported from leaves as the substrate for metabolism and growth. Sucrose and hexoses derived from it are also signalling molecules that modulate growth and development, but the importance for signalling of endogenous changes in sugar levels is poorly understood. We report that reduced activity of cytosolic invertase, which converts sucrose to hexoses, leads to pronounced metabolic, growth and developmental defects in roots of Arabidopsis (Arabidopsis thaliana) seedlings. In addition to altered sugar and downstream metabolite levels, roots of cinv1 cinv2 mutants have reduced elongation rates, cell and meristem size, abnormal meristematic cell division patterns, and altered expression of thousands of genes of diverse functions. Provision of exogenous glucose to mutant roots repairs relatively few of the defects. The extensive transcriptional differences between mutant and wild-type roots have hallmarks of both high sucrose and low hexose signalling. We conclude that the mutant phenotype reflects both low carbon availability for metabolism and growth and complex sugar signals derived from elevated sucrose and depressed hexose levels in the cytosol of mutant roots. Such reciprocal changes in endogenous sucrose and hexose levels potentially provide rich information about sugar status that translates into flexible adjustments of growth and development.

scholarly journals Inner Ear and Muscle Developmental Defects in Smpx-Deficient Zebrafish Embryos

2021 ◽  
Vol 22 (12) ◽  
pp. 6497
Author(s):  
Anna Ghilardi ◽  
Alberto Diana ◽  
Renato Bacchetta ◽  
Nadia Santo ◽  
Miriam Ascagni ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Hair Cells ◽  
Muscle Fibers ◽  
Underlying Mechanism ◽  
Loss Of Function ◽  
Zebrafish Model ◽  
Developmental Defects ◽  
Inner Ear Development ◽  
Syndromic Hearing Loss

The last decade has witnessed the identification of several families affected by hereditary non-syndromic hearing loss (NSHL) caused by mutations in the SMPX gene and the loss of function has been suggested as the underlying mechanism. In the attempt to confirm this hypothesis we generated an Smpx-deficient zebrafish model, pointing out its crucial role in proper inner ear development. Indeed, a marked decrease in the number of kinocilia together with structural alterations of the stereocilia and the kinocilium itself in the hair cells of the inner ear were observed. We also report the impairment of the mechanotransduction by the hair cells, making SMPX a potential key player in the construction of the machinery necessary for sound detection. This wealth of evidence provides the first possible explanation for hearing loss in SMPX-mutated patients. Additionally, we observed a clear muscular phenotype consisting of the defective organization and functioning of muscle fibers, strongly suggesting a potential role for the protein in the development of muscle fibers. This piece of evidence highlights the need for more in-depth analyses in search for possible correlations between SMPX mutations and muscular disorders in humans, thus potentially turning this non-syndromic hearing loss-associated gene into the genetic cause of dysfunctions characterized by more than one symptom, making SMPX a novel syndromic gene.

scholarly journals Loss of histone methyltransferase ASH1L in the developing mouse brain causes autistic-like behaviors

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yuen Gao ◽  
Natalia Duque-Wilckens ◽  
Mohammad B. Aljazi ◽  
Yan Wu ◽  
Adam J. Moeser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Brain ◽  
Molecular Mechanisms ◽  
Gene Mutations ◽  
Autism Spectrum ◽  
Normal Brain ◽  
Critical Function ◽  
Developmental Defects ◽  
Neurodevelopmental Disease ◽  
Developing Mouse Brain

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Recent genetic and clinical studies report that mutations of the epigenetic gene ASH1L are highly associated with human ASD and intellectual disability (ID). However, the causality and underlying molecular mechanisms linking ASH1L mutations to genesis of ASD/ID remain undetermined. Here we show loss of ASH1L in the developing mouse brain is sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory. Gene expression analyses uncover critical roles of ASH1L in regulating gene expression during neural cell development. Thus, our study establishes an ASD/ID mouse model revealing the critical function of an epigenetic factor ASH1L in normal brain development, a causality between Ash1L mutations and ASD/ID-like behaviors in mice, and potential molecular mechanisms linking Ash1L mutations to brain functional abnormalities.

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