Functions of SMC2 in the Development of Zebrafish Liver.

Xixi Li,Zongbin Cui,Qing Li,Yasong Zhao,Guili Song,Jing Ren

doi:10.3390/biomedicines9091240

Abstract

SMC2 (structural maintenance of chromosomes 2) is the core subunit of condensins, which play a central role in chromosome organization and segregation. However, the functions of SMC2 in embryonic development remain poorly understood, due to the embryonic lethality of homozygous SMC2−/− mice. Herein, we explored the roles of SMC2 in the liver development of zebrafish. The depletion of SMC2, with the CRISPR/Cas9-dependent gene knockout approach, led to a small liver phenotype. The specification of hepatoblasts was unaffected. Mechanistically, extensive apoptosis occurred in the liver of SMC2 mutants, which was mainly associated with the activation of the p53-dependent apoptotic pathway. Moreover, an aberrant activation of a series of apoptotic pathways in SMC2 mutants was involved in the defective chromosome segregation and subsequent DNA damage. Therefore, our findings demonstrate that SMC2 is necessary for zebrafish liver development.

Highlights

The zebrafish genome contains a single copy of each gene encoding subunits of condensin I and II complexes, and the amino acid identity between zebrafish and their human counterparts ranged from 36.5 to 74.2% (Table S2), indicating that the two SMC2-containing complexes are highly conserved among vertebrates
The loss of SMC2 led to a small liver phenotype in SMC2−/− mutants
Increased cell apoptosis and decreased cell proliferation are responsible for the small liver phenotype in SMC2−/− mutants

Summary

Introduction

Biomedicines 2021, 9, Chromosomes undergo essential changes in morphology, to control the proper expression of genes, and these changes are partially mediated by the structural maintenance of chromosome (SMC) proteins [1]. SMC proteins were initially found in Saccharomyces cerevisiae, and later in all tested eukaryotes [3]. Bacteria contain a single gene that encodes a single SMC protein to form homodimers [4]. At least six members of the SMC protein family are found in individual organisms. The primary structure of SMC proteins consists of the following five distinct domains: two nucleotide-binding motifs, Walker A and Walker B motifs that are located in the highly conserved N-terminal and C-terminal domains, respectively, and the central domain, which is composed of a moderately conserved “hinge” sequence that is flanked by two long coiled-coil motifs [5]

Methods

Results

Conclusion