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Dissection of bone morphogenetic protein signaling using genome-engineering tools

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Bone Morphogenetic Proteins: From Local to Systemic Therapeutics

Part of the book series: Progress in Inflammation Research ((PIR))

Abstract

Bone morphogenetic proteins (BMPs) encompass a large subgroup of evolutionary conserved, secreted signaling molecules belonging to the TGF-β superfamily. In contrast to that suggested by their name, BMP function is not restricted to the skeleton. Recent studies in several organisms have revealed multiple roles for BMPs during embryogenesis where they are involved in early embryonic pattering, gastrulation, tissue induction and differentiation [1]. BMP signaling activity is regulated at multiple levels (Fig. 1A). In the intracellular space multiple regulatory proteins control BMP signaling after initial BMP receptor activation. In the extracellular space BMP antagonists such as Noggin, Follistatin and related proteins, Gremlin and other members of the Dan family, Chordin and its relatives along with Twisted Gastrulation (Tsg), all regulate the ability of BMPs to engage the BMP receptors. Studies on flies and lower vertebrates have led to the concept that these extracellular interactions result in the formation of BMP activity gradients, which in turn provide positional cues to the cells that encounter them [2–4]. Although direct evidence for the operation of such activity gradients is missing in higher vertebrates, orthologs for all antagonists do exist. In addition, there are data pointing to neighboring or overlapping domains of expression between BMPs and their antagonists as well as evidence for BMP-dependent expression of the latter (for review see [5]). Therefore, when trying to understand BMP function in vivo, it is important to examine BMPs in the context of expression of their antagonists as well as other regulatory molecules.

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Authors and Affiliations

  1. Institute of Immunology, Biomedical Sciences Center ‘Al. Fleming’, 34 Al. Fleming Street, 16672, Vari, Greece

    Daniel Graf

  2. Genome Engineering Technologies, Regeneron Pharmaceuticals, Inc., 777 Old Saw River Road, Tarrytown, NY, 10591, USA

    Aris N. Economides

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  1. Daniel Graf
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  1. School of Medicine Inst. Anatomy Drago Perovic, University of Zagreb, Salata 11, 10000, Zagreb, Croatia

    Slobodan Vukicevic

  2. Genzyme Corporation, One Mountain Road, Framingham, MA, 01701-9322, USA

    Kuber T. Sampath

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Graf, D., Economides, A.N. (2008). Dissection of bone morphogenetic protein signaling using genome-engineering tools. In: Vukicevic, S., Sampath, K.T. (eds) Bone Morphogenetic Proteins: From Local to Systemic Therapeutics. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-8552-1_7

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  • DOI: https://doi.org/10.1007/978-3-7643-8552-1_7

  • Publisher Name: Birkhäuser Basel

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  • Online ISBN: 978-3-7643-8552-1

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