scholarly journals Dosage-Dependent Effects of Akt1/Protein Kinase Bα (PKBα) and Akt3/PKBγ on Thymus, Skin, and Cardiovascular and Nervous System Development in Mice

2005 ◽  
Vol 25 (23) ◽  
pp. 10407-10418 ◽  
Author(s):  
Zhong-Zhou Yang ◽  
Oliver Tschopp ◽  
Nicolas Di-Poï ◽  
Elisabeth Bruder ◽  
Anne Baudry ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Cycle Progression ◽  
System Development ◽  
Critical Role ◽  
Nervous System Development ◽  
Mouse Development ◽  
Double Knockout ◽  
Developmental Defects ◽  
Regulation Of Metabolism ◽  
Survival And Development

ABSTRACT Akt/protein kinase B (PKB) plays a critical role in the regulation of metabolism, transcription, cell migration, cell cycle progression, and cell survival. The existence of viable knockout mice for each of the three isoforms suggests functional redundancy. We generated mice with combined mutant alleles of Akt1 and Akt3 to study their effects on mouse development. Here we show that Akt1 − / − Akt3 +/ − mice display multiple defects in the thymus, heart, and skin and die within several days after birth, while Akt1 +/ − Akt3 − / − mice survive normally. Double knockout (Akt1 − / − Akt3 − / −) causes embryonic lethality at around embryonic days 11 and 12, with more severe developmental defects in the cardiovascular and nervous systems. Increased apoptosis was found in the developing brain of double mutant embryos. These data indicate that the Akt1 gene is more essential than Akt3 for embryonic development and survival but that both are required for embryo development. Our results indicate isoform-specific and dosage-dependent effects of Akt on animal survival and development.

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 Vitamin E is necessary for zebrafish nervous system development

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Brian Head ◽  
Jane La Du ◽  
Robyn L. Tanguay ◽  
Chrissa Kioussi ◽  
Maret G. Traber
Keyword(s):  
Nervous System ◽  
Vitamin E ◽  
System Development ◽  
Regulatory Protein ◽  
Nervous System Development ◽  
Developmental Defects ◽  
Transfer Protein ◽  
Rna In Situ Hybridization ◽  
Brain Ventricle

Abstract Vitamin E (VitE) deficiency results in embryonic lethality. Knockdown of the gene ttpa encoding for the VitE regulatory protein [α-tocopherol transfer protein (α-TTP)] in zebrafish embryos causes death within 24 h post-fertilization (hpf). To test the hypothesis that VitE, not just α-TTP, is necessary for nervous system development, adult 5D strain zebrafish, fed either VitE sufficient (E+) or deficient (E−) diets, were spawned to obtain E+ and E− embryos, which were subjected to RNA in situ hybridization and RT-qPCR. Ttpa was expressed ubiquitously in embryos up to 12 hpf. Early gastrulation (6 hpf) assessed by goosecoid expression was unaffected by VitE status. By 24 hpf, embryos expressed ttpa in brain ventricle borders, which showed abnormal closure in E− embryos. They also displayed disrupted patterns of paired box 2a (pax2a) and SRY-box transcription factor 10 (sox10) expression in the midbrain-hindbrain boundary, spinal cord and dorsal root ganglia. In E− embryos, the collagen sheath notochord markers (col2a1a and col9a2) appeared bent. Severe developmental errors in E− embryos were characterized by improper nervous system patterning of the usually carefully programmed transcriptional signals. Histological analysis also showed developmental defects in the formation of the fore-, mid- and hindbrain and somites of E− embryos at 24 hpf. Ttpa expression profile was not altered by the VitE status demonstrating that VitE itself, and not ttpa, is required for development of the brain and peripheral nervous system in this vertebrate embryo model.

scholarly journals Rybp/DEDAF Is Required for Early Postimplantation and for Central Nervous System Development

2005 ◽  
Vol 25 (16) ◽  
pp. 7193-7202 ◽  
Author(s):  
Melinda K. Pirity ◽  
Joseph Locker ◽  
Nicole Schreiber-Agus
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
System Development ◽  
Embryonic Stem ◽  
Physiological Role ◽  
Giant Cells ◽  
Nervous System Development ◽  
Neural Tube Closure ◽  
Central Nervous System Development ◽  
Mouse Development

ABSTRACT The Rybp/DEDAF protein has been implicated in both transcriptional regulation and apoptotic signaling, but its precise molecular function is unclear. To determine the physiological role of Rybp, we analyzed its expression during mouse development and generated mice carrying a targeted deletion of Rybp using homologous recombination in embryonic stem cells. Rybp was found to be broadly expressed during embryogenesis and was particularly abundant in extraembryonic tissues, including trophoblast giant cells. Consistent with this result, rybp homozygous null embryos exhibited lethality at the early postimplantation stage. At this time, Rybp was essential for survival of the embryo, for the establishment of functional extraembryonic structures, and for the execution of full decidualization. Through the use of a chimeric approach, the embryonic lethal phenotype was circumvented and a role for Rybp in central nervous system development was uncovered. Specifically, the presence of Rybp-deficient cells resulted in marked forebrain overgrowth and in localized regions of disrupted neural tube closure. Functions for Rybp in the brain also were supported by the finding of exencephaly in about 15% of rybp heterozygous mutant embryos, and by Rybp's distinct neural expression pattern. Together, these findings support critical roles for Rybp at multiple stages of mouse embryogenesis.

scholarly journals E2f3a and E2f3b Contribute to the Control of Cell Proliferation and Mouse Development

2008 ◽  
Vol 29 (2) ◽  
pp. 414-424 ◽  
Author(s):  
Jean-Leon Chong ◽  
Shih-Yin Tsai ◽  
Nidhi Sharma ◽  
Rene Opavsky ◽  
Richard Price ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Specific Gene ◽  
Mouse Development ◽  
Double Knockout ◽  
Proliferation And Apoptosis ◽  
The Individual ◽  
Redundant Functions

ABSTRACT The E2f3 locus encodes two Rb-binding gene products, E2F3a and E2F3b, which are differentially regulated during the cell cycle and are thought to be critical for cell cycle progression. We targeted the individual inactivation of E2f3a or E2f3b in mice and examined their contributions to cell proliferation and development. Chromatin immunoprecipitation and gene expression experiments using mouse embryo fibroblasts deficient in each isoform showed that E2F3a and E2F3b contribute to G1/S-specific gene expression and cell proliferation. Expression of E2f3a or E2f3b was sufficient to support E2F target gene expression and cell proliferation in the absence of other E2F activators, E2f1 and E2f2, suggesting that these isoforms have redundant functions. Consistent with this notion, E2f3a −/− and E2f3b −/− embryos developed normally, whereas embryos lacking both isoforms (E2f3 −/−) died in utero. We also find that E2f3a and E2f3b have redundant and nonredundant roles in the context of Rb mutation. Analysis of double-knockout embryos suggests that the ectopic proliferation and apoptosis in Rb −/− embryos is mainly mediated by E2f3a in the placenta and nervous system and by both E2f3a and E2f3b in lens fiber cells. Together, we conclude that the contributions of E2F3a and E2F3b in cell proliferation and development are context dependent.

scholarly journals Interaction Between the Complement System and Infectious Agents – A Potential Mechanistic Link to Neurodegeneration and Dementia

2021 ◽  
Vol 15 ◽  
Author(s):  
Noriko Shinjyo ◽  
Wataru Kagaya ◽  
Marcela Pekna
Keyword(s):  
Nervous System ◽  
Complement System ◽  
Complement Activation ◽  
Neural Plasticity ◽  
Measles Virus ◽  
System Development ◽  
Critical Role ◽  
Nervous System Development ◽  
Infectious Agents ◽  
The Complement System

As part of the innate immune system, complement plays a critical role in the elimination of pathogens and mobilization of cellular immune responses. In the central nervous system (CNS), many complement proteins are locally produced and regulate nervous system development and physiological processes such as neural plasticity. However, aberrant complement activation has been implicated in neurodegeneration, including Alzheimer’s disease. There is a growing list of pathogens that have been shown to interact with the complement system in the brain but the short- and long-term consequences of infection-induced complement activation for neuronal functioning are largely elusive. Available evidence suggests that the infection-induced complement activation could be protective or harmful, depending on the context. Here we summarize how various infectious agents, including bacteria (e.g., Streptococcus spp.), viruses (e.g., HIV and measles virus), fungi (e.g., Candida spp.), parasites (e.g., Toxoplasma gondii and Plasmodium spp.), and prion proteins activate and manipulate the complement system in the CNS. We also discuss the potential mechanisms by which the interaction between the infectious agents and the complement system can play a role in neurodegeneration and dementia.

scholarly journals Extracellular Matrix-Associated Protein Sc1 Is Not Essential for Mouse Development

2000 ◽  
Vol 20 (2) ◽  
pp. 656-660 ◽  
Author(s):  
Peter J. McKinnon ◽  
Susan K. McLaughlin ◽  
Manuela Kapsetaki ◽  
Robert F. Margolskee
Keyword(s):  
Extracellular Matrix ◽  
Nervous System ◽  
Gene Targeting ◽  
System Development ◽  
Nervous System Development ◽  
Mouse Development ◽  
Term Survival ◽  
Insight Into ◽  
Developing Nervous System

ABSTRACT Sc1 is an extracellular matrix-associated protein whose function is unknown. During early embryonic development, Sc1 is widely expressed, and from embryonic day 12 (E12), Sc1 is expressed primarily in the developing nervous system. This switch in Sc1 expression at E12 suggests an importance for nervous-system development. To gain insight into Sc1 function, we used gene targeting to inactivate mouse Sc1. The Sc1-null mice showed no obvious deficits in any organs. These mice were born at the expected ratios, were fertile, and had no obvious histological abnormalities, and their long-term survival did not differ from littermate controls. Therefore, the function of Sc1 during development is not critical or, in its absence, is subserved by another protein.

scholarly journals aPKC in neuronal differentiation, maturation and function

2019 ◽  
Vol 3 (3) ◽  
Author(s):  
Sophie M. Hapak ◽  
Carla V. Rothlin ◽  
Sourav Ghosh
Keyword(s):  
Nervous System ◽  
Protein Kinase ◽  
Neural Development ◽  
System Development ◽  
Nervous System Development ◽  
Versus Gene ◽  
Metabolic Functions ◽  
Neuropsychiatric Diseases ◽  
And Function ◽  
Neuronal Functions

Abstract The atypical Protein Kinase Cs (aPKCs)—PRKCI, PRKCZ and PKMζ—form a subfamily within the Protein Kinase C (PKC) family. These kinases are expressed in the nervous system, including during its development and in adulthood. One of the aPKCs, PKMζ, appears to be restricted to the nervous system. aPKCs are known to play a role in a variety of cellular responses such as proliferation, differentiation, polarity, migration, survival and key metabolic functions such as glucose uptake, that are critical for nervous system development and function. Therefore, these kinases have garnered a lot of interest in terms of their functional role in the nervous system. Here we review the expression and function of aPKCs in neural development and in neuronal maturation and function. Despite seemingly paradoxical findings with genetic deletion versus gene silencing approaches, we posit that aPKCs are likely candidates for regulating many important neurodevelopmental and neuronal functions, and may be associated with a number of human neuropsychiatric diseases.

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