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

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

doi:10.1016/j.devcel.2014.09.018

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

Full Record
Other Related Research

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:: 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

Publication Date:: 2014-11-01

Research Org.:: Lawrence Berkeley National Laboratory (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.

Copy to clipboard


                    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.  https://doi.org/10.1016/j.devcel.2014.09.018

Copy to clipboard


                    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.  https://doi.org/10.1016/j.devcel.2014.09.018.

Copy to clipboard


                    
@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}

}

Copy to clipboard

Journal Article:

Free Publicly Available Full Text

Publisher's Version of Record
https://doi.org/10.1016/j.devcel.2014.09.018

Other availability

Search WorldCat to find libraries that may hold this journal

Citation Metrics:

Cited by: 68 works

Citation information provided by
Web of Science

Save / Share:

Export Metadata

Save to My Library

Similar Records in DOE PAGES and OSTI.GOV collections:

SMAD4 target genes are part of a transcriptional network that integrates the response to BMP and SHH signaling during early limb bud patterning

Journal Article Gamart, Julie ; Barozzi, Iros ; Laurent, Frédéric ; ... - Development (Cambridge)

SMAD4 regulates gene expression in response to BMP and TGFβ signal transduction, and is required for diverse morphogenetic processes, but its target genes have remained largely elusive. Here, we identify the SMAD4 target genes in mouse limb buds using an epitope-tagged Smad4 allele for ChIP-seq analysis in combination with transcription profiling. This analysis shows that SMAD4 predominantly mediates BMP signal transduction during early limb bud development. Unexpectedly, the expression of cholesterol biosynthesis enzymes is precociously downregulated and intracellular cholesterol levels are reduced in Smad4-deficient limb bud mesenchymal progenitors. Most importantly, our analysis reveals a predominant function of SMAD4 in upregulatingmore »« less
https://doi.org/10.1242/dev.200182

Full Text Available
Gli2 and Gli3 Localize to Cilia and Require the Intraflagellar Transport Protein Polaris for Processing and Function

Journal Article Michaud, III, Edward J ; Haycraft, Courtney J ; Aydin Son, Yesim ; ... - PLoS Genetics

Intraflagellar transport (IFT) proteins are essential for cilia assembly and have recently been associated with a number of developmental processes, such as left-right axis specification and limb and neural tube patterning. Genetic studies indicate that IFT proteins are required for Sonic hedgehog (Shh)signaling downstream of the Smoothened and Patched membrane proteins but upstream of the Glioma (Gli) transcription factors. However, the role that IFT proteins play in transduction of Shh signaling and the importance of cilia in this process remain unknown. Here we provide insights into the mechanism by which defects in an IFT protein, Tg737/Polaris, affect Shh signaling inmore »« less
Gli2 and Gli3 Localize to Cilia and Require the Intraflagellar Transport Protein Polaris for Processing and Function

Journal Article Haycraft, Courtney J. ; Banizs, Boglarka ; Aydin-Son, Yesim ; ... - PLoS Genetics

Intraflagellar transport (IFT) proteins are essential for cilia assembly and have recently been associated with a number of developmental processes, such as left–right axis specification and limb and neural tube patterning. Genetic studies indicate that IFT proteins are required for Sonic hedgehog (Shh) signaling downstream of the Smoothened and Patched membrane proteins but upstream of the Glioma (Gli) transcription factors. However, the role that IFT proteins play in transduction of Shh signaling and the importance of cilia in this process remain unknown. Here we provide insights into the mechanism by which defects in an IFT protein, Tg737/Polaris, affect Shh signalingmore »« less
https://doi.org/10.1371/journal.pgen.0010053

Full Text Available
HAND2 Target Gene Regulatory Networks Control Atrioventricular Canal and Cardiac Valve Development

Journal Article Laurent, Frédéric ; Girdziusaite, Ausra ; Gamart, Julie ; ... - Cell Reports

The HAND2 transcriptional regulator controls cardiac development, and we uncover additional essential functions in the endothelial to mesenchymal transition (EMT) underlying cardiac cushion development in the atrioventricular canal (AVC). In Hand2-deficient mouse embryos, the EMT underlying AVC cardiac cushion formation is disrupted, and we combined ChIP-seq of embryonic hearts with transcriptome analysis of wild-type and mutants AVCs to identify the functionally relevant HAND2 target genes. The HAND2 target gene regulatory network (GRN) includes most genes with known functions in EMT processes and AVC cardiac cushion formation. One of these is Snai1, an EMT master regulator whose expression is lost frommore »« less
Cited by 34
https://doi.org/10.1016/j.celrep.2017.05.004
Fgf16 is essential for pectoral fin bud formation in zebrafish

Journal Article Nomura, Ryohei ; Kamei, Eriko ; Hotta, Yuuhei ; ... - Biochemical and Biophysical Research Communications

Zebrafish pectoral fin bud formation is an excellent model for studying morphogenesis. Fibroblast growth factors (Fgfs) and sonic hedgehog (shh) are essential for pectoral fin bud formation. We found that Fgf16 was expressed in the apical ectodermal ridge (AER) of fin buds. A knockdown of Fgf16 function resulted in no fin bud outgrowth. Fgf16 is required for cell proliferation and differentiation in the mesenchyme and the AER of the fin buds, respectively. Fgf16 functions downstream of Fgf10, a mesenchymal factor, signaling to induce the expression of Fgf4 and Fgf8 in the AER. Fgf16 in the AER and shh in themore »« less
https://doi.org/10.1016/j.bbrc.2006.06.108

Similar Records