HAND2 targets define a network of transcriptional regulators that compartmentalize the early limb bud mesenchyme

Marco Osterwalder; Dario Speziale; Malak Shoukry; Rajiv Mohan; Robert Ivanek; Manuel Kohler; Christian Beisel; Xiaohui Wen; Suzie J. Scales; Vincent M. Christoffels; Axel Visel; Javier Lopez-Rios; Rolf Zeller

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

HAND2 targets define a network of transcriptional regulators that compartmentalize the early limb bud mesenchyme

Marco Osterwalder, Dario Speziale, Malak Shoukry, Rajiv Mohan, Robert Ivanek, Manuel Kohler, Christian Beisel, Xiaohui Wen, Suzie J. Scales, Vincent M. Christoffels, Axel Visel, Javier Lopez-Rios, Rolf Zeller

Research output: Contribution to journal › Article › Academic › peer-review

80 Citations (Scopus)

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. Our analysis uncovers the transcriptional circuits that function in establishing distinct mesenchymal compartments downstream of HAND2 and upstream of SHH signaling

Original language	English
Pages (from-to)	345-357
Journal	Developmental Cell
Volume	31
Issue number	3
DOIs	https://doi.org/10.1016/j.devcel.2014.09.018
Publication status	Published - 2014

Access to Document

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

Cite this

Osterwalder, M., Speziale, D., Shoukry, M., Mohan, R., Ivanek, R., Kohler, M., Beisel, C., Wen, X., Scales, S. J., Christoffels, V. M., Visel, A., Lopez-Rios, J., & Zeller, R. (2014). HAND2 targets define a network of transcriptional regulators that compartmentalize the early limb bud mesenchyme. Developmental Cell, 31(3), 345-357. https://doi.org/10.1016/j.devcel.2014.09.018

@article{5de75ac480ed41bf906284fa9554b0be,

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. Our analysis uncovers the transcriptional circuits that function in establishing distinct mesenchymal compartments downstream of HAND2 and upstream of SHH signaling",

author = "Marco Osterwalder and Dario Speziale and Malak Shoukry and Rajiv Mohan and Robert Ivanek and Manuel Kohler and Christian Beisel and Xiaohui Wen and Scales, {Suzie J.} and Christoffels, {Vincent M.} and Axel Visel and Javier Lopez-Rios and Rolf Zeller",

year = "2014",

doi = "https://doi.org/10.1016/j.devcel.2014.09.018",

language = "English",

volume = "31",

pages = "345--357",

journal = "Developmental Cell",

issn = "1534-5807",

publisher = "Cell Press",

number = "3",

}

Osterwalder, M, Speziale, D, Shoukry, M, Mohan, R, Ivanek, R, Kohler, M, Beisel, C, Wen, X, Scales, SJ, Christoffels, VM, Visel, A, Lopez-Rios, J & Zeller, R 2014, 'HAND2 targets define a network of transcriptional regulators that compartmentalize the early limb bud mesenchyme', Developmental Cell, vol. 31, no. 3, pp. 345-357. https://doi.org/10.1016/j.devcel.2014.09.018

TY - JOUR

T1 - HAND2 targets define a network of transcriptional regulators that compartmentalize the early limb bud mesenchyme

AU - Osterwalder, Marco

AU - Speziale, Dario

AU - Shoukry, Malak

AU - Mohan, Rajiv

AU - Ivanek, Robert

AU - Kohler, Manuel

AU - Beisel, Christian

AU - Wen, Xiaohui

AU - Scales, Suzie J.

AU - Christoffels, Vincent M.

AU - Visel, Axel

AU - Lopez-Rios, Javier

AU - Zeller, Rolf

PY - 2014

Y1 - 2014

N2 - 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. Our analysis uncovers the transcriptional circuits that function in establishing distinct mesenchymal compartments downstream of HAND2 and upstream of SHH signaling

AB - 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. Our analysis uncovers the transcriptional circuits that function in establishing distinct mesenchymal compartments downstream of HAND2 and upstream of SHH signaling

U2 - https://doi.org/10.1016/j.devcel.2014.09.018

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

M3 - Article

C2 - 25453830

SN - 1534-5807

VL - 31

SP - 345

EP - 357

JO - Developmental Cell

JF - Developmental Cell

IS - 3

ER -