Regulation of SOX9 by HOXD13 may be related to the occurrence of congenital foot malformation

doi:10.13418/j.issn.1001-165x.2020.06.013

Chinese Journal of Clinical Anatomy ›› 2020, Vol. 38 ›› Issue (6) : 691-696. DOI: 10.13418/j.issn.1001-165x.2020.06.013

WANG Zheng-dong¹, YAN Nan¹, LIU Li-ying², LI Shu¹, CHEN Yao¹, KONG Si-hui¹,LI Pei-yuan¹, JIN Chun-lian³

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Abstract

Objective　To study the molecular mechanism of HOXD13 and SOX9 genes in the occurrence of foot soft tissue malformation of idiopathic congenital talipes equinovarus (ICTEV).　Methods 3 HOXD13 binding sites upstream of 5 'of SOX9 gene were predicted by the software, and luciferase activity of serial truncated and mutant vector in promoter region of SOX9 gene was detected. The binding effect of HOXD13 to the 3 sites of SOX9 gene promoter was verified by ChIP in vivo. The expression levels of HOXD13 and SOX9 were detected by qRT-PCR.　Results　A negative regulatory region between -1158 to -770 bp (site 1) and -512 to -368 bp (site 3) in the upstream of SOX9 gene 5' was found by the Luciferase. Between -770 and -512bp (locus 2) was a positive regulatory region. ChIP results showed that HOXD13 could bind to SOX9 locus 3.The mRNA expression of SOX9 gene was up-regulated by interference of HOXD13 expression.　Conclusions　The expression of SOX9 gene was up-regulated by HOXD13 in combination with the negative regulation region of SOX9 gene 5' upstream. The interference of HOXD13 up-regulated SOX9 gene expression may be related to the occurrence of soft tissue contracture on the ankle of foot.

Key words

Congenital foot deformity / 　HOXD13 / 　SOX9 / 　Development / 　Regulation

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WANG Zheng-dong, YAN Nan, LIU Li-ying, LI Shu, CHEN Yao, KONG Si-hui, LI Pei-yuan, JIN Chun-lian. Regulation of SOX9 by HOXD13 may be related to the occurrence of congenital foot malformation[J]. Chinese Journal of Clinical Anatomy. 2020, 38(6): 691-696 https://doi.org/10.13418/j.issn.1001-165x.2020.06.013

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