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      Pathways involved in pony body size development

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          Abstract

          Background

          The mechanism of body growth in mammals is poorly understood. Here, we investigated the regulatory networks involved in body growth through transcriptomic analysis of pituitary and epiphyseal tissues of smaller sized Debao ponies and Mongolian horses at the juvenile and adult stages.

          Results

          We found that growth hormone receptor ( GHR) was expressed at low levels in long bones, although g rowth hormone ( GH) was highly expressed in Debao ponies compared with Mongolian horses. Moreover, significant downregulated of the GHR pathway components m-RAS and ATF3 was found in juvenile ponies, which slowed the proliferation of bone osteocytes. However, WNT2 and PLCβ2 were obviously upregulated in juvenile Debao ponies, which led to premature mineralization of the bone extracellular matrix. Furthermore, we found that the WNT/Ca 2+ pathway may be responsible for regulating body growth. GHR was demonstrated by q-PCR and Western blot analyses to be expressed at low levels in long bones of Debao ponies. Treatment with WNT antagonistI decreased the expression of WNT pathway components ( P < 0.05) in vitro. Transduction of ATDC5 cells with a GHR-RNAi lentiviral vector decreased the expression of the GHR pathway components ( P < 0.05). Additionally, the expression of the IGF-1 gene in the liver was lower in Debao ponies than in Mongolian horses at the juvenile and adult stages. Detection of plasma hormone concentrations showed that Debao ponies expressed higher levels of IGF-1 as juveniles and higher levels of GH as adults than Mongolian horses, indicating that the hormone regulation in Debao ponies differs from that in Mongolian horses.

          Conclusion

          Our work provides insights into the genetic regulation of short stature growth in mammals and can provide useful information for the development of therapeutic strategies for small size.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12864-020-07323-1.

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          Most cited references63

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          edgeR: a Bioconductor package for differential expression analysis of digital gene expression data

          Summary: It is expected that emerging digital gene expression (DGE) technologies will overtake microarray technologies in the near future for many functional genomics applications. One of the fundamental data analysis tasks, especially for gene expression studies, involves determining whether there is evidence that counts for a transcript or exon are significantly different across experimental conditions. edgeR is a Bioconductor software package for examining differential expression of replicated count data. An overdispersed Poisson model is used to account for both biological and technical variability. Empirical Bayes methods are used to moderate the degree of overdispersion across transcripts, improving the reliability of inference. The methodology can be used even with the most minimal levels of replication, provided at least one phenotype or experimental condition is replicated. The software may have other applications beyond sequencing data, such as proteome peptide count data. Availability: The package is freely available under the LGPL licence from the Bioconductor web site (http://bioconductor.org). Contact: mrobinson@wehi.edu.au
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            Salmon: fast and bias-aware quantification of transcript expression using dual-phase inference

            We introduce Salmon, a method for quantifying transcript abundance from RNA-seq reads that is accurate and fast. Salmon is the first transcriptome-wide quantifier to correct for fragment GC content bias, which we demonstrate substantially improves the accuracy of abundance estimates and the reliability of subsequent differential expression analysis. Salmon combines a new dual-phase parallel inference algorithm and feature-rich bias models with an ultra-fast read mapping procedure.
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              Osteoclast differentiation and activation.

              Osteoclasts are specialized cells derived from the monocyte/macrophage haematopoietic lineage that develop and adhere to bone matrix, then secrete acid and lytic enzymes that degrade it in a specialized, extracellular compartment. Discovery of the RANK signalling pathway in the osteoclast has provided insight into the mechanisms of osteoclastogenesis and activation of bone resorption, and how hormonal signals impact bone structure and mass. Further study of this pathway is providing the molecular basis for developing therapeutics to treat osteoporosis and other diseases of bone loss.
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                Author and article information

                Contributors
                yanru1964@163.com
                huanminzhou@263.net
                Journal
                BMC Genomics
                BMC Genomics
                BMC Genomics
                BioMed Central (London )
                1471-2164
                18 January 2021
                18 January 2021
                2021
                : 22
                : 58
                Affiliations
                GRID grid.411638.9, ISNI 0000 0004 1756 9607, College of Life Sciences, , Inner Mongolia Agricultural University, ; No. 306 Zhaowuda Road, Hohhot, 010018 China
                Author information
                http://orcid.org/0000-0003-3852-0071
                Article
                7323
                10.1186/s12864-020-07323-1
                7814589
                1945f719-0593-4306-9814-0ccde36450a7
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 2 March 2020
                : 14 December 2020
                Funding
                Funded by: Showa University
                Funded by: All Japan Labor Welfare Foundation
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2021

                Genetics
                growth hormone receptor,debao pony,rna-seq,short stature
                Genetics
                growth hormone receptor, debao pony, rna-seq, short stature

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