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Title: HAND2 Targets Define a Network of Transcriptional Regulators that Compartmentalize the Early Limb Bud Mesenchyme

Abstract

The genetic networks that govern vertebrate development are well studied, but how the interactions of trans-acting factors with cis-regulatory modules (CRMs) are integrated into spatiotemporal regulation of gene expression is not clear. The transcriptional regulator HAND2 is required during limb, heart, and branchial arch development. Here, we identify the genomic regions enriched in HAND2 chromatin complexes from mouse embryos and limb buds. Then we analyze the HAND2 target CRMs in the genomic landscapes encoding transcriptional regulators required in early limb buds. HAND2 controls the expression of genes functioning in the proximal limb bud and orchestrates the establishment of anterior and posterior polarity of the nascent limb bud mesenchyme by impacting Gli3 and Tbx3 expression. TBX3 is required downstream of HAND2 to refine the posterior Gli3 expression boundary. In conclusion, our analysis uncovers the transcriptional circuits that function in establishing distinct mesenchymal compartments downstream of HAND2 and upstream of SHH signaling.

Authors:
; ; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1225559
Alternate Identifier(s):
OSTI ID: 1222383; OSTI ID: 1257829
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Published Article
Journal Name:
Developmental Cell
Additional Journal Information:
Journal Name: Developmental Cell Journal Volume: 31 Journal Issue: 3; Journal ID: ISSN 1534-5807
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Osterwalder, Marco, Speziale, Dario, Shoukry, Malak, Mohan, Rajiv, Ivanek, Robert, Kohler, Manuel, Beisel, Christian, Wen, Xiaohui, Scales, Suzie J., Christoffels, Vincent M., Visel, Axel, Lopez-Rios, Javier, and Zeller, Rolf. HAND2 Targets Define a Network of Transcriptional Regulators that Compartmentalize the Early Limb Bud Mesenchyme. United States: N. p., 2014. Web. doi:10.1016/j.devcel.2014.09.018.
Osterwalder, Marco, Speziale, Dario, Shoukry, Malak, Mohan, Rajiv, Ivanek, Robert, Kohler, Manuel, Beisel, Christian, Wen, Xiaohui, Scales, Suzie J., Christoffels, Vincent M., Visel, Axel, Lopez-Rios, Javier, & Zeller, Rolf. HAND2 Targets Define a Network of Transcriptional Regulators that Compartmentalize the Early Limb Bud Mesenchyme. United States. doi:10.1016/j.devcel.2014.09.018.
Osterwalder, Marco, Speziale, Dario, Shoukry, Malak, Mohan, Rajiv, Ivanek, Robert, Kohler, Manuel, Beisel, Christian, Wen, Xiaohui, Scales, Suzie J., Christoffels, Vincent M., Visel, Axel, Lopez-Rios, Javier, and Zeller, Rolf. Sat . "HAND2 Targets Define a Network of Transcriptional Regulators that Compartmentalize the Early Limb Bud Mesenchyme". United States. doi:10.1016/j.devcel.2014.09.018.
@article{osti_1225559,
title = {HAND2 Targets Define a Network of Transcriptional Regulators that Compartmentalize the Early Limb Bud Mesenchyme},
author = {Osterwalder, Marco and Speziale, Dario and Shoukry, Malak and Mohan, Rajiv and Ivanek, Robert and Kohler, Manuel and Beisel, Christian and Wen, Xiaohui and Scales, Suzie J. and Christoffels, Vincent M. and Visel, Axel and Lopez-Rios, Javier and Zeller, Rolf},
abstractNote = {The genetic networks that govern vertebrate development are well studied, but how the interactions of trans-acting factors with cis-regulatory modules (CRMs) are integrated into spatiotemporal regulation of gene expression is not clear. The transcriptional regulator HAND2 is required during limb, heart, and branchial arch development. Here, we identify the genomic regions enriched in HAND2 chromatin complexes from mouse embryos and limb buds. Then we analyze the HAND2 target CRMs in the genomic landscapes encoding transcriptional regulators required in early limb buds. HAND2 controls the expression of genes functioning in the proximal limb bud and orchestrates the establishment of anterior and posterior polarity of the nascent limb bud mesenchyme by impacting Gli3 and Tbx3 expression. TBX3 is required downstream of HAND2 to refine the posterior Gli3 expression boundary. In conclusion, our analysis uncovers the transcriptional circuits that function in establishing distinct mesenchymal compartments downstream of HAND2 and upstream of SHH signaling.},
doi = {10.1016/j.devcel.2014.09.018},
journal = {Developmental Cell},
number = 3,
volume = 31,
place = {United States},
year = {2014},
month = {11}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1016/j.devcel.2014.09.018

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Cited by: 29 works
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