RA Acts in a Coherent Feed-Forward Mechanism with Tbx5 to Control Limb Bud Induction and Initiation

Satoko Nishimoto; Susan M. Wilde; Sophie Wood; Malcolm P O Logan

doi:10.1016/j.celrep.2015.06.068

RA Acts in a Coherent Feed-Forward Mechanism with Tbx5 to Control Limb Bud Induction and Initiation

Satoko Nishimoto, Susan M. Wilde, Sophie Wood, Malcolm P O Logan^*

^*Corresponding author for this work

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

49 Citations (Scopus)

Abstract

The retinoic acid (RA)- and β-catenin-signaling pathways regulate limb bud induction and initiation; however, their mechanisms of action are not understood and have been disputed. We demonstrate that both pathways are essential and that RA and β-catenin/TCF/LEF signaling act cooperatively with Hox gene inputs to directly regulate Tbx5 expression. Furthermore, in contrast to previous models, we show that Tbx5 and Tbx4 expression in forelimb and hindlimb, respectively, are not sufficient for limb outgrowth and that input from RA is required. Collectively, our data indicate that RA signaling and Tbx genes act in a coherent feed-forward loop to regulate Fgf10 expression and, as a result, establish a positive feedback loop of FGF signaling between the limb mesenchyme and ectoderm. Our results incorporate RA-, β-catenin/TCF/LEF-, and FGF-signaling pathways into a regulatory network acting to recruit cells of the embryo flank to become limb precursors.

Original language	English
Pages (from-to)	879-891
Number of pages	13
Journal	Cell Reports
Volume	12
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2015.06.068
Publication status	Published - 4 Aug 2015

Access to Document

10.1016/j.celrep.2015.06.068

Cite this

@article{8f2a20eb1bdb4ee28b57695a85cb5b13,

title = "RA Acts in a Coherent Feed-Forward Mechanism with Tbx5 to Control Limb Bud Induction and Initiation",

abstract = "The retinoic acid (RA)- and β-catenin-signaling pathways regulate limb bud induction and initiation; however, their mechanisms of action are not understood and have been disputed. We demonstrate that both pathways are essential and that RA and β-catenin/TCF/LEF signaling act cooperatively with Hox gene inputs to directly regulate Tbx5 expression. Furthermore, in contrast to previous models, we show that Tbx5 and Tbx4 expression in forelimb and hindlimb, respectively, are not sufficient for limb outgrowth and that input from RA is required. Collectively, our data indicate that RA signaling and Tbx genes act in a coherent feed-forward loop to regulate Fgf10 expression and, as a result, establish a positive feedback loop of FGF signaling between the limb mesenchyme and ectoderm. Our results incorporate RA-, β-catenin/TCF/LEF-, and FGF-signaling pathways into a regulatory network acting to recruit cells of the embryo flank to become limb precursors.",

author = "Satoko Nishimoto and Wilde, {Susan M.} and Sophie Wood and Logan, {Malcolm P O}",

year = "2015",

month = aug,

day = "4",

doi = "10.1016/j.celrep.2015.06.068",

language = "English",

volume = "12",

pages = "879--891",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Elsevier BV",

number = "5",

}

TY - JOUR

T1 - RA Acts in a Coherent Feed-Forward Mechanism with Tbx5 to Control Limb Bud Induction and Initiation

AU - Nishimoto, Satoko

AU - Wilde, Susan M.

AU - Wood, Sophie

AU - Logan, Malcolm P O

PY - 2015/8/4

Y1 - 2015/8/4

N2 - The retinoic acid (RA)- and β-catenin-signaling pathways regulate limb bud induction and initiation; however, their mechanisms of action are not understood and have been disputed. We demonstrate that both pathways are essential and that RA and β-catenin/TCF/LEF signaling act cooperatively with Hox gene inputs to directly regulate Tbx5 expression. Furthermore, in contrast to previous models, we show that Tbx5 and Tbx4 expression in forelimb and hindlimb, respectively, are not sufficient for limb outgrowth and that input from RA is required. Collectively, our data indicate that RA signaling and Tbx genes act in a coherent feed-forward loop to regulate Fgf10 expression and, as a result, establish a positive feedback loop of FGF signaling between the limb mesenchyme and ectoderm. Our results incorporate RA-, β-catenin/TCF/LEF-, and FGF-signaling pathways into a regulatory network acting to recruit cells of the embryo flank to become limb precursors.

AB - The retinoic acid (RA)- and β-catenin-signaling pathways regulate limb bud induction and initiation; however, their mechanisms of action are not understood and have been disputed. We demonstrate that both pathways are essential and that RA and β-catenin/TCF/LEF signaling act cooperatively with Hox gene inputs to directly regulate Tbx5 expression. Furthermore, in contrast to previous models, we show that Tbx5 and Tbx4 expression in forelimb and hindlimb, respectively, are not sufficient for limb outgrowth and that input from RA is required. Collectively, our data indicate that RA signaling and Tbx genes act in a coherent feed-forward loop to regulate Fgf10 expression and, as a result, establish a positive feedback loop of FGF signaling between the limb mesenchyme and ectoderm. Our results incorporate RA-, β-catenin/TCF/LEF-, and FGF-signaling pathways into a regulatory network acting to recruit cells of the embryo flank to become limb precursors.

UR - http://www.scopus.com/inward/record.url?scp=84938556850&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2015.06.068

DO - 10.1016/j.celrep.2015.06.068

M3 - Article

AN - SCOPUS:84938556850

SN - 2211-1247

VL - 12

SP - 879

EP - 891

JO - Cell Reports

JF - Cell Reports

IS - 5

ER -

RA Acts in a Coherent Feed-Forward Mechanism with Tbx5 to Control Limb Bud Induction and Initiation

Abstract

Access to Document

Other files and links

Fingerprint

Cite this