International Journal of Molecular Sciences

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Dear Colleagues,

Due to the accessibility and generalization of the CRISPR-Cas9 system in any laboratory setting, in recent years, it has seen tremendous demand for the understanding of various diseases at the level of molecular genetics. Zebrafish has evolved as a crucial model organism that has been utilized in almost all fields of biomedical research. In particular, forward genetics, performed using zebrafish development, has been fruitful in identifying genes that give rise to distinct phenotypes when functionally abnormal. At present, it is possible to pinpoint the phenotype in response to a single gene mutation, with the discovery of the most advanced “reverse-genetics” tool, which becomes much more powerful in a clinical setting when combined with the depth of next-generation sequencing technology.

In this Special Issue, we invite manuscripts in the format of a research article or a review in the field of zebrafish modeling in genetics and genomics to improve human diseases.

Prof. Dr. Seong-kyu Choe
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (1 paper)

Research

22 pages, 18125 KiB

Open AccessArticle

Functional and Genetic Analyses Unveil the Implication of CDC27 in Hemifacial Microsomia

by Wenjie Song, Xin Xia, Yue Fan, Bo Zhang and Xiaowei Chen

Int. J. Mol. Sci. 2024, 25(9), 4707; https://doi.org/10.3390/ijms25094707 - 26 Apr 2024

Viewed by 598

Abstract

Hemifacial microsomia (HFM) is a rare congenital genetic syndrome primarily affecting the first and second pharyngeal arches, leading to defects in the mandible, external ear, and middle ear. The pathogenic genes remain largely unidentified. Whole-exome sequencing (WES) was conducted on 12 HFM probands and their unaffected biological parents. Predictive structural analysis of the target gene was conducted using PSIPRED (v3.3) and SWISS-MODEL, while STRING facilitated protein-to-protein interaction predictions. CRISPR/Cas9 was applied for gene knockout in zebrafish. In situ hybridization (ISH) was employed to examine the spatiotemporal expression of the target gene and neural crest cell (NCC) markers. Immunofluorescence with PH3 and TUNEL assays were used to assess cell proliferation and apoptosis. RNA sequencing was performed on mutant and control embryos, with rescue experiments involving target mRNA injections and specific gene knockouts. CDC27 was identified as a novel candidate gene for HFM, with four nonsynonymous de novo variants detected in three unrelated probands. Structural predictions indicated significant alterations in the secondary and tertiary structures of CDC27. cdc27 knockout in zebrafish resulted in craniofacial malformation, spine deformity, and cardiac edema, mirroring typical HFM phenotypes. Abnormalities in somatic cell apoptosis, reduced NCC proliferation in pharyngeal arches, and chondrocyte differentiation issues were observed in cdc27^−/− mutants. cdc27 mRNA injections and cdkn1a or tp53 knockout significantly rescued pharyngeal arch cartilage dysplasia, while sox9a mRNA administration partially restored the defective phenotypes. Our findings suggest a functional link between CDC27 and HFM, primarily through the inhibition of CNCC proliferation and disruption of pharyngeal chondrocyte differentiation. Full article

(This article belongs to the Special Issue Zebrafish: A Powerful Model for Genetics and Genomics 3.0)

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