A unique stylopod patterning mechanism by Shox2-controlled osteogenesis

Ye, Wenduo; Song, Yingnan; Huang, Zhen; Osterwalder, Marco; Ljubojevic, Anja; Xu, Jue; Bobick, Brent; Abassah-Oppong, Samuel; Ruan, Ningsheng; Shamby, Ross; Yu, Diankun; Zhang, Lu; Cai, Chen -Leng; Visel, Axel; Zhang, Yanding; Cobb, John; Chen, YiPing

doi:10.1242/dev.138750

Title: A unique stylopod patterning mechanism by Shox2-controlled osteogenesis

Journal Article · Fri Jun 10 00:00:00 EDT 2016 · Development (Cambridge)

DOI:https://doi.org/10.1242/dev.138750· OSTI ID:1393061

Ye, Wenduo ^[1]; Song, Yingnan ^[2]; Huang, Zhen ^[2]; Osterwalder, Marco ^[3]; Ljubojevic, Anja ^[4]; Xu, Jue ^[5]; Bobick, Brent ^[4]; Abassah-Oppong, Samuel ^[4]; Ruan, Ningsheng ^[2]; Shamby, Ross ^[1]; Yu, Diankun ^[1]; Zhang, Lu ^[6]; Cai, Chen -Leng ^[6]; Visel, Axel ^[7]; Zhang, Yanding ^[8]; Cobb, John ^[4];

^[2]

Tulane Univ., New Orleans, LA (United States)
Tulane Univ., New Orleans, LA (United States); Fujian Normal Univ., Fujian (People's Republic of China)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Univ. of Calgary, Calgary, AB (Canada)
Tulane Univ., New Orleans, LA (United States); Sichuan Univ., Sichuan (People's Republic of China)
Icahn School of Medicine at Mount Sinai, New York, NY (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Univ. of California, Merced, CA (United States)
Fujian Normal Univ., Fujian (People's Republic of China)

Here, vertebrate appendage patterning is programmed by Hox-TALE factorbound regulatory elements. However, it remains unclear which cell lineages are commissioned by Hox-TALE factors to generate regional specific patterns and whether other Hox-TALE co-factors exist. In this study, we investigated the transcriptional mechanisms controlled by the Shox2 transcriptional regulator in limb patterning. Harnessing an osteogenic lineage-specific Shox2 inactivation approach we show that despite widespread Shox2 expression in multiple cell lineages, lack of the stylopod observed upon Shox2 deficiency is a specific result of Shox2 loss of function in the osteogenic lineage. ChIP-Seq revealed robust interaction of Shox2 with cis-regulatory enhancers clustering around skeletogenic genes that are also bound by Hox-TALE factors, supporting a lineage autonomous function of Shox2 in osteogenic lineage fate determination and skeleton patterning. Pbx ChIP-Seq further allowed the genome-wide identification of cis-regulatory modules exhibiting co-occupancy of Pbx, Meis and Shox2 transcriptional regulators. Integrative analysis of ChIP-Seq and RNA-Seq data and transgenic enhancer assays indicate that Shox2 patterns the stylopod as a repressor via interaction with enhancers active in the proximal limb mesenchyme and antagonizes the repressive function of TALE factors in osteogenesis.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

DOE Contract Number:: AC02-05CH11231

OSTI ID:: 1393061

Journal Information:: Development (Cambridge), Vol. 143, Issue 14; ISSN 0950-1991

Publisher:: Company of Biologists

Country of Publication:: United States

Language:: English

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