Isl1 and Ldb Co-regulators of transcription are essential early determinants of mouse limb development

Authors

  • Ginat Narkis,

    Corresponding author
    1. Laboratory of Mammalian Genes and Development, Program in Genomics of Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
    • Laboratory of Mammalian Genes and Development, Program in Genomics of Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892

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  • Itai Tzchori,

    1. Laboratory of Mammalian Genes and Development, Program in Genomics of Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
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  • Tsadok Cohen,

    1. Laboratory of Mammalian Genes and Development, Program in Genomics of Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
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  • Alex Holtz,

    1. Laboratory of Mammalian Genes and Development, Program in Genomics of Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
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  • Eric Wier,

    1. Laboratory of Mammalian Genes and Development, Program in Genomics of Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
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  • Heiner Westphal

    1. Laboratory of Mammalian Genes and Development, Program in Genomics of Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
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  • This article is a US Government work and, as such, is in the public domain of the United States of America.

Abstract

Background: The developing limb has served as an excellent model for studying pattern formation and signal transduction in mammalians. Many of the crucial genes that regulate growth and patterning of the limb following limb bud formation are now well known. However, details regarding the control of limb initiation and early stages of outgrowth remain to be defined. This report is focused on genetic events that pave the way for the establishment of a hindlimb bud. Results: Fgf10 and Tbx are crucial for early phases of limb bud initiation. Here we show that in the absence of Isl1 or of Ldb1/2, there is no hindlimb bud development. Fgf10 expression in the bud mesenchyme is dependent on Isl1 and its Ldb co-regulators. Conclusions: Thus, Isl1 and the Ldb co-regulators of transcription are essential early determinants of mouse limb development. Isl1/Ldb complexes regulate Fgf10 to orchestrate the earliest stages of hindlimb formation. Developmental Dynamics 241:787–791, 2012. Published 2012 Wiley Periodicals, Inc.

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