The expression of Gli3, regulated by HOXD13, may play a role in idiopathic congenital talipes equinovarus.

BMC Musculoskeletal Disorders
DongHua CaoNing Zhao

Abstract

Idiopathic congenital talipes equinovarus (ICTEV) is a congenital limb deformity. Based on extended transmission disequilibrium testing, Gli-Kruppel family member 3 (Gli3) has been identified as a candidate gene for ICTEV. Here, we verify the role of Gli3 in ICTEV development. Using the rat ICTEV model, we analyzed the differences in Gli3 expression levels between model rats and normal control rats. We used luciferase reporter gene assays and ChIP/EMSA assays to analyze the regulatory elements of Gli3. Gli3 showed higher expression levels in ICTEV model rats compared to controls (P < 0.05). We identified repressor and activator regions in the rat Gli3 promoter. The Gli3 promoter also contains two putative Hoxd13 binding sites. Using EMSA, the Hoxd13 binding site 2 was found to directly interact with Hoxd13 in vitro. ChIP assays of the Hoxd13-Gli3 promoter complex from a developing limb confirmed that endogenous Hoxd13 interacts with this region in vivo. Our findings suggest that HoxD13 directly interacts with the promoter of Gli3. The increase of Gli3 expression in ICTEV model animal might result from the low expression of HoxD13.

References

Oct 1, 1977·Analytical Biochemistry·V F Kalb, R W Bernlohr
Aug 1, 1988·Molecular and Cellular Biology·J M RuppertB Vogelstein
May 1, 1972·Clinical Orthopaedics and Related Research·R Wynne-Davies
Jun 29, 1995·Nature·A P DavisM R Capecchi
May 1, 1997·Matrix Biology : Journal of the International Society for Matrix Biology·M WeedB R Olsen
Nov 14, 1997·Nature Genetics·U RadhakrishnaS E Antonarakis
Mar 13, 1999·The Journal of Biological Chemistry·P DaiS Ishii
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·S H ShinL G Biesecker
Sep 28, 1999·Trends in Genetics : TIG·A Ruiz i Altaba
Mar 10, 2000·Journal of Pediatric Orthopedics. Part B·E Delgado-BaezaA Martos-Rodríguez
Sep 9, 2000·Journal of Medical Genetics·C ChapmanR O Nicol
Nov 1, 2001·Annual Review of Cell and Developmental Biology·J Capdevila, J C Izpisúa Belmonte
Aug 2, 2002·Clinical Orthopaedics and Related Research·Fred Dietz
Oct 31, 2002·Development·Jianwu Bai, Denise Montell
Aug 12, 2004·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Maria Félix BastidaMaria A Ros
Aug 31, 2004·Human Molecular Genetics·Andrea N AlbrechtStefan Mundlos
Mar 1, 2005·Clinical Genetics·F R DietzJ C Murray

❮ Previous
Next ❯

Citations

Sep 21, 2013·Circulation Research·Marie-Ange RenaultAlain-Pierre Gadeau
Dec 21, 2012·Molecular Medicine Reports·Zhengdong WangChunlian Jin
Aug 24, 2018·Journal of Orthopaedic Surgery and Research·Vito PavoneGianluca Testa

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
PCR
electrophoresis
Assay
immunoprecipitation
ChIP

Software Mentioned

Match

Related Concepts

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Aphasia

Aphasia affects the ability to process language, including formulation and comprehension of language and speech, as well as the ability to read or write. Here is the latest research on aphasia.

Related Papers

The Journal of Bone and Joint Surgery. British Volume
M B S BrewsterI D Dunn-van der Ploeg
The Journal of Bone and Joint Surgery. American Volume
Geoffrey F HaftHaemish A Crawford
The Journal of Bone and Joint Surgery. American Volume
Christof RadlerF Grill
© 2022 Meta ULC. All rights reserved