scholarly journals Molecular mechanisms of embryonic tail development in the self-fertilizing mangrove killifish Kryptolebias marmoratus

Development ◽  
2021 ◽  
Vol 148 (24) ◽  
Author(s):  
Hussein A. Saud ◽  
Paul A. O'Neill ◽  
Yosuke Ono ◽  
Bas Verbruggen ◽  
Ronny Van Aerle ◽  
...  

ABSTRACT Using the self-fertilizing mangrove killifish, we characterized two mutants, shorttail (stl) and balltail (btl). These mutants showed abnormalities in the posterior notochord and muscle development. Taking advantage of a highly inbred isogenic strain of the species, we rapidly identified the mutated genes, noto and msgn1 in the stl and btl mutants, respectively, using a single lane of RNA sequencing without the need of a reference genome or genetic mapping techniques. Next, we confirmed a conserved morphant phenotype in medaka and demonstrate a crucial role of noto and msgn1 in cell sorting between the axial and paraxial part of the tail mesoderm. This novel system could substantially accelerate future small-scale forward-genetic screening and identification of mutations. Therefore, the mangrove killifish could be used as a complementary system alongside existing models for future molecular genetic studies.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 377-377
Author(s):  
Sandra Stehling-Sun ◽  
Rebecca Jimenez ◽  
Andrew Hu ◽  
Fernando D. Camargo

Abstract MEF2 transcription factors are well-established regulators of muscle development. Recently, work in murine models has identified one of these factors, Mef2c, as an important regulator in the pathogenesis and the development of acute myeloid leukemia (AML). However, little is know about the molecular mechanism and physiological role of Mef2c in hematopoiesis. Using conditional gene ablation, we have discovered an unexpected role for MEF2c in hematopoietic stem cells (HSCs), where it is required for pan-lymphoid commitment. Competitive repopulation experiments using Mef2c-null HSCs deleted by means of the Mx1-Cre/poly(IC) approach, revealed completely normal monocytic, granulocytic and erythroid differentiation capacities by mutant cells. Generation and renewal of myeloid progenitors and HSCs was also normal. However, contribution to lymphoid lineages (T-cells, B-cells and natural killer cells) was dramatically reduced. Mef2c-deleted HSCs were able to generate lymphoid primed multipotent progenitors (LMPPs) and expressed normal levels of Flt-3 and the master lymphoid regulator ikaros. However, expression of the interleukin-7 receptor (IL-7R) and the number of phenotypically defined common lymphoid progenitors (CLPs) were substantially reduced. We have found two conserved Mef2c-binding sites in the promoter of the Il-7R gene, indicating that Mef2c could directly regulate Il-7R transcription. This and other potential molecular mechanisms of Mef2c-mediated lymphoid commitment will be discussed. We have also studied the effects of lineage-specific deletion of Mef2c in both myeloid and lymphoid populations. Whereas deletion in myelomonocytic cells using the LysM-Cre strain resulted in no anomalies, B-cell specific ablation with the CD19-Cre line revealed major phenotypical and functional abnormalities. CD19-Cre:Mef2cf/f mice show impaired germinal center formation and reduced antibody production in response to T-cell dependent antigens. In addition Mef2c-null mature B-cells fail to express the mature marker CD23, the low affinity receptor for IgE, which we show is a direct transcriptional target. As a consequence of CD23 reduction, CD19-Cre:Mef2cf/f mice have increased IgE production, thus indicating a potential role of Mef2c in allergic disease. Our work here sheds new light on the molecular mechanisms of lymphopoiesis and identifies MEF2 factors as critical hematopoietic transcriptional regulators.


2006 ◽  
Vol 97 (5) ◽  
pp. 508-513 ◽  
Author(s):  
Mark Mackiewicz ◽  
Andrey Tatarenkov ◽  
Andrew Perry ◽  
J. Ryce Martin ◽  
John F. Elder ◽  
...  

2011 ◽  
Vol 240 (10) ◽  
pp. spcone-spcone
Author(s):  
Sulayman Mourabit ◽  
Mathew Edenbrow ◽  
Darren P. Croft ◽  
Tetsuhiro Kudoh

2011 ◽  
Vol 2 (2) ◽  
Author(s):  
Monojit Debnath ◽  
Karen Doyle ◽  
Camilla Langan ◽  
Colm McDonald ◽  
Brian Leonard ◽  
...  

AbstractPsychiatric disorders are common and complex and their precise biological underpinnings remain elusive. Multiple epidemiological, molecular, genetic and gene expression studies suggest that immune system dysfunction may contribute to the risk for developing psychiatric disorders including schizophrenia, bipolar disorder, and major depressive disorder. However, the precise mechanisms by which inflammation-related events confer such risk are unclear. In this review, we examine the peripheral and central evidence for inflammation in psychiatric disorders and the potential molecular mechanisms implicated including inhibition of neurogenesis, apoptosis, the HPA-axis, the role of brain-derived neurotrophic factor and the interplay between the glutamatergic, dopaminergic and serotonergic neurotransmitter systems.


2008 ◽  
Vol 86 (9) ◽  
pp. 976-982 ◽  
Author(s):  
Yukino Nakamura ◽  
Koushirou Suga ◽  
Yoshitaka Sakakura ◽  
Takashi Sakamoto ◽  
Atsushi Hagiwara

The populations of the only known self-fertilizing vertebrate Kryptolebias marmoratus (Poey, 1880) (formerly known as Rivulus marmoratus Poey, 1880; Cyprinodontiformes: Aplocheilidae) usually consist of different homozygous lineages; however, heterozygous individuals are found occasionally and ratios of homozygosity and heterozygosity in populations are dependent on the proportion of males. However, it is still unclear what impact male-mediated genetic diversity has on the phenotype of K. marmoratus. To clarify this, we attempted outcrossing between male and hermaphrodite of two different clonal strains with different life-history traits using artificial insemination, and examined the genotypes and growth of the hybrid F2 generation. We detected genetic differences between the two clonal strains using amplified fragment length polymorphism (AFLP) analysis with 3 primer combinations, and then obtained 11 AFLP markers. From a total of 31 artificial inseminations with two clonal strains, 1 of 13 hatched fish clearly indicated heterozygosity. The hybrid F2 generations were also heterozygous. Moreover, the growths of the hybrid F2 generation were intermediate of the parental strains from days 0 to 30. Therefore, outcrossing changes genetic architecture and the new genotypes potentially result in new phenotypes of the subsequent generations of K. marmoratus. It may also play a role in adaptation to new environments and the facilitation of local adaptation.


Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 596
Author(s):  
Nguyen Truong Co ◽  
Mai Suan Li

The self-assembly of amyloidogenic peptides and proteins into fibrillar structures has been intensively studied for several decades, because it seems to be associated with a number of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease. Therefore, understanding the molecular mechanisms of this phenomenon is important for identifying an effective therapy for the corresponding diseases. Protein aggregation in living organisms very often takes place on surfaces like membranes and the impact of a surface on this process depends not only on the surface chemistry but also on its topology. Our goal was to develop a simple lattice model for studying the role of surface roughness in the aggregation kinetics of polypeptide chains and the morphology of aggregates. We showed that, consistent with the experiment, an increase in roughness slows down the fibril formation, and this process becomes inhibited at a very highly level of roughness. We predicted a subtle catalytic effect that a slightly rough surface promotes the self-assembly of polypeptide chains but does not delay it. This effect occurs when the interaction between the surface and polypeptide chains is moderate and can be explained by taking into account the competition between energy and entropy factors.


2011 ◽  
Vol 240 (7) ◽  
pp. 1694-1704 ◽  
Author(s):  
Sulayman Mourabit ◽  
Mathew Edenbrow ◽  
Darren P. Croft ◽  
Tetsuhiro Kudoh

2006 ◽  
Vol 53 (4) ◽  
pp. 427-430 ◽  
Author(s):  
Yoshitaka Sakakura ◽  
Kiyoshi Soyano ◽  
David L.G. Noakes ◽  
Atsushi Hagiwara

2021 ◽  
Vol 13 ◽  
Author(s):  
Mohammad Reza Asadi ◽  
Mehdi Hassani ◽  
Shiva Kiani ◽  
Hani Sabaie ◽  
Marziyeh Sadat Moslehian ◽  
...  

LncRNAs act as part of non-coding RNAs at high levels of complex and stimulatory configurations in basic molecular mechanisms. Their extensive regulatory activity in the CNS continues on a small scale, from the functions of synapses to large-scale neurodevelopment and cognitive functions, aging, and can be seen in both health and disease situations. One of the vast consequences of the pathological role of dysregulated lncRNAs in the CNS due to their role in a network of regulatory pathways can be manifested in Alzheimer's as a neurodegenerative disease. The disease is characterized by two main hallmarks: amyloid plaques due to the accumulation of β-amyloid components and neurofibrillary tangles (NFT) resulting from the accumulation of phosphorylated tau. Numerous studies in humans, animal models, and various cell lines have revealed the role of lncRNAs in the pathogenesis of Alzheimer's disease. This scoping review was performed with a six-step strategy and based on the Prisma guideline by systematically searching the publications of seven databases. Out of 1,591 records, 69 articles were utterly aligned with the specified inclusion criteria and were summarized in the relevant table. Most of the studies were devoted to BACE1-AS, NEAT1, MALAT1, and SNHG1 lncRNAs, respectively, and about one-third of the studies investigated a unique lncRNA. About 56% of the studies reported up-regulation, and 7% reported down-regulation of lncRNAs expressions. Overall, this study was conducted to investigate the association between lncRNAs and Alzheimer's disease to make a reputable source for further studies and find more molecular therapeutic goals for this disease.


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