Integrative Analyses of miRNA-mRNA Interactions Reveal let-7b, miR-128 and MAPK Pathway Involvement in Muscle Mass Loss in Sex-Linked Dwarf Chickens.

Wen Luo,Guihuan Li,Xiquan Zhang,Shumao Lin,Qinghua Nie

doi:10.3390/ijms17030276

Abstract

The sex-linked dwarf (SLD) chicken is an ideal model system for understanding growth hormone (GH)-action and growth hormone receptor (GHR) function because of its recessive mutation in the GHR gene. Skeletal muscle mass is reduced in the SLD chicken with a smaller muscle fiber diameter. Our previous study has presented the mRNA and miRNA expression profiles of the SLD chicken and normal chicken between embryo day 14 and seven weeks of age. However, the molecular mechanism of GHR-deficient induced muscle mass loss is still unclear, and the key molecules and pathways underlying the GHR-deficient induced muscle mass loss also remain to be illustrated. Here, by functional network analysis of the differentially expressed miRNAs and mRNAs between the SLD and normal chickens, we revealed that let-7b, miR-128 and the MAPK pathway might play key roles in the GHR-deficient induced muscle mass loss, and that the reduced cell division and growth are potential cellular processes during the SLD chicken skeletal muscle development. Additionally, we also found some genes and miRNAs involved in chicken skeletal muscle development, through the MAPK, PI3K-Akt, Wnt and Insulin signaling pathways. This study provides new insights into the molecular mechanism underlying muscle mass loss in the SLD chickens, and some regulatory networks that are crucial for chicken skeletal muscle development.

Highlights

The sex-linked dwarf (SLD) chicken is caused by a recessive mutation of the growth hormone receptor (GHR) gene located on the Z chromosome
From the expression profiles and validation assays we found that let-7b may be involved in higher GHR mRNA expression levels in the SLD chickens than in normal chickens, and that let-7b may function in the regulation of many signaling pathways through its direct target gene GHR [31]
Considering that our previous data have shown that the leg muscle weight in embryo day 14 (E14) normal chickens is heavier than that in the SLD chickens, it is possible that the skeletal muscle development of these two strains has become different from the embryonic stage on

Summary

Introduction

The sex-linked dwarf (SLD) chicken is caused by a recessive mutation of the growth hormone receptor (GHR) gene located on the Z chromosome This mutation results in a number of phenotypic and physiological alterations of the SLD chickens. Shorter shanks, lower basal metabolism, higher serum growth hormone (GH), lower serum insulin-like growth factor-1 (IGF-1), higher tolerance to heat and higher feed conversion rate of SLD chickens are observed compared to those of normal chickens [1,2,3]. Another significant phenotypic change of SLD chickens is that the average body weight of homozygous (dwdw) chickens was about 40% lower than that of normal chickens [3,4,5]. The precise molecular mechanism of how the GHR gene mutations caused so many phenotypic and physiological alterations still remains unclear, and the core regulatory pathways and gene interactional networks underlying dwarfism need to be further explored

Results

Discussion

Conclusion