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Dear Colelagues,

The development of organisms involves the regulation of patterns in gene expression. Those patterns are often set in a heritable condition through epigenetic modifications and associated pathways of cellular memory. In this way, the widespread synchronization in genetic patterns of expression ultimately determines cellular differentiation and developmental consequences during embryogenesis. Epigenetic aberrations are known to be associated with a range of developmental diseases and, in mature tissues, can also be associated with tumorigenic events. For this special issue, we invite papers related to the molecular, cellular, and developmental significance of epigenetics during embryological development as well as developmental and oncological diseases associated with epigenetic aberrations.

Dr. Mark Brown
Guest Editor

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Keywords

epigenetics
embryogenesis
developmental biology
epigenetic aberrations

Published Papers (3 papers)

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Research

7 pages, 971 KiB

Open AccessArticle

The Lysine Methyltransferase SMYD2 Is Required for Definite Hematopoietic Stem Cell Production in the Mouse Embryo

and

Vet. Sci. 2020, 7(3), 100; https://doi.org/10.3390/vetsci7030100 - 25 Jul 2020

Cited by 2 | Viewed by 2860

Abstract

The five-membered SET and MYND domain-containing lysine methyltransferase (SMYD) family plays pivotal roles in development and differentiation. Initially characterized within the cardiovascular system, one such member, SMYD2, has been implicated in transcriptional and apoptotic regulation of hematopoiesis. Deletion of Smyd2 in adult mouse Hemaopoietic Stem Cells (HSC) using an interferon-inducible mx1-Cre-mediated conditional knockout (CKO) led to HSC reduction via both apoptosis and transcriptional deficiencies. Since HSC are specified from hemogenic endothelial (HE) cells in the dorsal aorta (DA), we sought to determine whether the flaw in HSC originated embryologically from this site. Toward this end, we performed deletion with vav-Cre mice, which is active in all hematopoietic and endothelial tissues from E10.5 embryonic life onward. Unexpectedly, we observed no defects in the embryo, other than apoptotic loss of definite HSC, whereas adult hematopoietic populations downstream were unaffected. These results further establish the importance of SMYD2 in antiapoptotic gene control of gene expression from the embryo to the adult. Full article

(This article belongs to the Special Issue Epigenetic Factors of Embryological Development and Tumorigenesis)

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9 pages, 1865 KiB

Open AccessCommunication

Characterizing the Role of SMYD2 in Mammalian Embryogenesis—Future Directions

and

Vet. Sci. 2020, 7(2), 63; https://doi.org/10.3390/vetsci7020063 - 12 May 2020

Cited by 5 | Viewed by 3459

Abstract

The SET and MYND domain-containing (SMYD) family of lysine methyltransferases are essential in several mammalian developmental pathways. Although predominantly expressed in the heart, the role of SMYD2 in heart development has yet to be fully elucidated and has even been shown to be dispensable in a murine Nkx2-5-associated conditional knockout. Additionally, SMYD2 was recently shown to be necessary not only for lymphocyte development but also for the viability of hematopoietic leukemias. Based on the broad expression pattern of SMYD2 in mammalian tissues, it is likely that it plays pivotal roles in a host of additional normal and pathological processes. In this brief review, we consider what is currently known about the normal and pathogenic functions of SMYD2 and propose specific future directions for characterizing its role in embryogenesis. Full article

(This article belongs to the Special Issue Epigenetic Factors of Embryological Development and Tumorigenesis)

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15 pages, 2185 KiB

Open AccessArticle

Nitric Oxide as a Potential Adjuvant Therapeutic for Neuroblastoma: Effects of NO on Murine N2a Cells

Jenna L. Gordon

Melissa M. Reynolds

and

Mark A. Brown

Vet. Sci. 2020, 7(2), 51; https://doi.org/10.3390/vetsci7020051 - 23 Apr 2020

Cited by 4 | Viewed by 3674

Abstract

Neuroblastoma, the most common extracranial solid tumor in children, accounts for 15% of all pediatric cancer deaths. Pharmaceutical applications of S-Nitrosylation, which, under normal conditions is involved with a host of epigenetic and embryological development pathways, have exhibited great potential for use as adjuvant therapeutics in the clinical management of cancer. Herein, an evaluation of the impact of nitric oxide (NO) as a potent anticancer agent on murine neuroblastoma cells is presented. Excitingly cell viability, colony formation, and non-carcinogenic cell analysis illustrate the significance and practicality of NO as a cytotoxic anticancer therapeutic. Resazurin, WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt), and MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphyltetrazolium bromide) assays consistently displayed a moderate, ~20–25% reduction in cell viability after exposure to 1 mM S-Nitrosoglutathione (GSNO). A colony formation assay demonstrated that treated cells no longer exhibited colony formation capacity. Identically GSNO-treated Adult Human Dermal Fibroblasts (HDFa) exhibited no decrease in viability, indicating potential discrimination between neoplastic and normal cells. Collectively, our findings indicate a potential application for NO as an adjuvant therapeutic in the clinical management of neuroblastoma. Full article

(This article belongs to the Special Issue Epigenetic Factors of Embryological Development and Tumorigenesis)

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