Pathways involved in pony body size development
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ABSTRACT:
PROVIDER: PRJNA609553 | ENA |
REPOSITORIES: ENA
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Project description:The mechanism of body growth in mammals is poorly understood. Here, we report the regulatory networks involved in body growth through analyzing transcriptomes of pituitary and epiphyseal tissues of Debao ponies and Mongolian horses at juvenile and adult stages. We found that GHR was expressed little in long bones though GH was highly expressed in Debao ponies compared with Mongolian horses. Moreover, m-RAS and ATF3, involved in the GHR pathway, were found to be significantly downregulated 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 bone extracellular matrix. Furthermore, we found that the WNT/Ca2+ pathway may be responsible for the regulation of body growth. We then demonstrated that GHR was lacking in long bones of Debao ponies using RT-qPCR and Western blot. Treatment with WNT antagonist 1 decreased expression of the WNT pathway (P≤0.05) in vitro. The transduction of ATDC5 cells with GHR-RNAi lentivirus decreased expression of the GHR pathway (P≤0.05). Additionally, detection of plasma hormone concentrations showed that the ponies had higher levels of IGF-1 as juveniles and GH in adulthood than Mongolian horses, indicating that the hormone regulation in Debao ponies differs from that in Mongolian horses. Our work provides an insight into the genetic regulation for dwarf growth in mammals and a reference for therapeutic strategy for dwarfism
2021-01-27 | GSE146145 | GEO
Project description:BackgroundThe 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.ResultsWe found that growth hormone receptor (GHR) was expressed at low levels in long bones, although growth 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 PLC?2 were obviously upregulated in juvenile Debao ponies, which led to premature mineralization of the bone extracellular matrix. Furthermore, we found that the WNT/Ca2+ 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.ConclusionOur 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.
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