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Signals in Embryonic Germ Layer Specification
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Signals in Embryonic Germ Layer Specification

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 8472

Special Issue Editor

Dr. Jaebong Kim

E-Mail Website
Guest Editor
Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University, Chuncheon, Gangwon-Do, Republic of Korea
Interests: embryonic development; germ layer formation; cell signaling

Special Issue Information

Dear Colleagues, 

The embryonic development of vertebrates is governed by several sets of evolutionarily conserved signals, including BMP, FGF, Activin, Nodal, and Wnt. These signals are integrated to orchestrate the cell fate determination, germ layer specification, and embryonic patterning through controlling the expression of the target gene(s) regulatory network (GRN). However, understanding the molecular crosstalk among various signaling pathway(s) and GRN remains to be fully elucidated. Hence, the scope of this Special Issue is to expand our knowledge of early embryogenic processes that are actively involved in the activation/deactivation of signal transduction and the target transcription factors (on different signals input) for fate determination and lineage priming during germ layer specification in vertebrates.

Dr. Jaebong Kim
Guest Editor

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Published Papers (3 papers)

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Research

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20 pages, 3452 KiB  
Article
Bmp4 Synexpression Gene, Sizzled, Transcription Is Collectively Modulated by Smad1 and Ventx1.1/Ventx2.1 in Early Xenopus Embryos
by Zia Ur Rehman, Faryal Tayyaba, Unjoo Lee and Jaebong Kim
Int. J. Mol. Sci. 2022, 23(21), 13335; https://doi.org/10.3390/ijms232113335 - 1 Nov 2022
Cited by 2 | Viewed by 2080
Abstract
Sizzled (Szl) is a secreted frizzled protein, having a sequence homology with the extracellular cysteine-rich domain (CRD) of the Wnt receptor, ‘Frizzled’. Contrary to the other secreted frizzled like proteins (Sfrps), szl belongs to the bone morphogenetic protein 4 (Bmp4) synexpression group and [...] Read more.
Sizzled (Szl) is a secreted frizzled protein, having a sequence homology with the extracellular cysteine-rich domain (CRD) of the Wnt receptor, ‘Frizzled’. Contrary to the other secreted frizzled like proteins (Sfrps), szl belongs to the bone morphogenetic protein 4 (Bmp4) synexpression group and is tightly coexpressed with Bmp4. What is not known is how the szl transcription achieves its Bmp4 synexpression pattern. To address the molecular details of szl transcription control, we cloned a promoter of size 1566 base pairs for szl (bps) from the Xenopus laevis genomic DNA. Luciferase and eGFP reporter gene results of this szl promoter (−1566 bp) in its activation and repression patterns by Bmp4/Smad1 and a dominant negative Bmp4 receptor (DNBR) were similar to those of the endogenous szl expression. Reporter gene assays and site-directed mutagenesis of the szl promoter mapped an active Bmp4/Smad1 response element (BRE) and a cis-acting element, which competitively share a direct binding site for Ventx1.1 and Ventx2.1 (a Ventx response element, VRE). Smad1 and ventx2.1 alone increased szl promoter activity; in addition, the binding of each protein component was enhanced with their coexpression. Interestingly, Ventx1.1 repressed this reporter gene activity; however, Ventx1.1 and Ventx2.1 together positively regulated the szl promoter activity. From our analysis, Ventx2.1 binding was enhanced by Ventx1.1, but Ventx1.1 inhibitory binding was inhibited by co-injection of Ventx2.1 for the VRE site. The inhibitory Ventx1.1 co-injection decreased Smad1 binding on the szl promoter. In a triple combination of overexpressed Smad1/Ventx1.1/Ventx2.1, the reduced binding of Smad1 from Ventx1.1 was recovered to that of the Smad1/Ventx2 combination. Collectively, this study provides evidence of Bmp4/Smad1 signaling for a primary immediate early response and its two oppositely behaving target transcription factors, Ventx1.1 and Ventx2.1, for a secondary response, as they together upregulate the szl promoter’s activity to achieve szl expression in a Bmp4 synexpression manner. Full article
(This article belongs to the Special Issue Signals in Embryonic Germ Layer Specification)
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20 pages, 4387 KiB  
Article
1H NMR Metabolite Monitoring during the Differentiation of Human Induced Pluripotent Stem Cells Provides New Insights into the Molecular Events That Regulate Embryonic Chondrogenesis
by Ashley Coope, Zain Ghanameh, Olivia Kingston, Carl M. Sheridan, Richard Barrett-Jolley, Marie M. Phelan and Rachel A. Oldershaw
Int. J. Mol. Sci. 2022, 23(16), 9266; https://doi.org/10.3390/ijms23169266 - 17 Aug 2022
Cited by 3 | Viewed by 2638
Abstract
The integration of cell metabolism with signalling pathways, transcription factor networks and epigenetic mediators is critical in coordinating molecular and cellular events during embryogenesis. Induced pluripotent stem cells (IPSCs) are an established model for embryogenesis, germ layer specification and cell lineage differentiation, advancing [...] Read more.
The integration of cell metabolism with signalling pathways, transcription factor networks and epigenetic mediators is critical in coordinating molecular and cellular events during embryogenesis. Induced pluripotent stem cells (IPSCs) are an established model for embryogenesis, germ layer specification and cell lineage differentiation, advancing the study of human embryonic development and the translation of innovations in drug discovery, disease modelling and cell-based therapies. The metabolic regulation of IPSC pluripotency is mediated by balancing glycolysis and oxidative phosphorylation, but there is a paucity of data regarding the influence of individual metabolite changes during cell lineage differentiation. We used 1H NMR metabolite fingerprinting and footprinting to monitor metabolite levels as IPSCs are directed in a three-stage protocol through primitive streak/mesendoderm, mesoderm and chondrogenic populations. Metabolite changes were associated with central metabolism, with aerobic glycolysis predominant in IPSC, elevated oxidative phosphorylation during differentiation and fatty acid oxidation and ketone body use in chondrogenic cells. Metabolites were also implicated in the epigenetic regulation of pluripotency, cell signalling and biosynthetic pathways. Our results show that 1H NMR metabolomics is an effective tool for monitoring metabolite changes during the differentiation of pluripotent cells with implications on optimising media and environmental parameters for the study of embryogenesis and translational applications. Full article
(This article belongs to the Special Issue Signals in Embryonic Germ Layer Specification)
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Review

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24 pages, 3318 KiB  
Review
Ventx Family and Its Functional Similarities with Nanog: Involvement in Embryonic Development and Cancer Progression
by Shiv Kumar, Vijay Kumar, Wenchang Li and Jaebong Kim
Int. J. Mol. Sci. 2022, 23(5), 2741; https://doi.org/10.3390/ijms23052741 - 1 Mar 2022
Cited by 5 | Viewed by 3178
Abstract
The Ventx family is one of the subfamilies of the ANTP (antennapedia) superfamily and belongs to the NK-like (NKL) subclass. Ventx is a homeobox transcription factor and has a DNA-interacting domain that is evolutionarily conserved throughout vertebrates. It has been extensively [...] Read more.
The Ventx family is one of the subfamilies of the ANTP (antennapedia) superfamily and belongs to the NK-like (NKL) subclass. Ventx is a homeobox transcription factor and has a DNA-interacting domain that is evolutionarily conserved throughout vertebrates. It has been extensively studied in Xenopus, zebrafish, and humans. The Ventx family contains transcriptional repressors widely involved in embryonic development and tumorigenesis in vertebrates. Several studies have documented that the Ventx family inhibited dorsal mesodermal formation, neural induction, and head formation in Xenopus and zebrafish. Moreover, Ventx2.2 showed functional similarities to Nanog and Barx1, leading to pluripotency and neural-crest migration in vertebrates. Among them, Ventx protein is an orthologue of the Ventx family in humans. Studies have demonstrated that human Ventx was strongly associated with myeloid-cell differentiation and acute myeloid leukemia. The therapeutic potential of Ventx family inhibition in combating cancer progression in humans is discussed. Additionally, we briefly discuss genome evolution, gene duplication, pseudo-allotetraploidy, and the homeobox family in Xenopus. Full article
(This article belongs to the Special Issue Signals in Embryonic Germ Layer Specification)
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