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Intracellular Communication among Morphogen Signaling Pathways during Vertebrate Body Plan Formation.

ABSTRACT: During embryonic development in vertebrates, morphogens play an important role in cell fate determination and morphogenesis. Bone morphogenetic proteins (BMPs) belonging to the transforming growth factor-? (TGF-?) family control the dorsal-ventral (DV) patterning of embryos, whereas other morphogens such as fibroblast growth factor (FGF), Wnt family members, and retinoic acid (RA) regulate the formation of the anterior-posterior (AP) axis. Activation of morphogen signaling results in changes in the expression of target genes including transcription factors that direct cell fate along the body axes. To ensure the correct establishment of the body plan, the processes of DV and AP axis formation must be linked and coordinately regulated by a fine-tuning of morphogen signaling. In this review, we focus on the interplay of various intracellular regulatory mechanisms and discuss how communication among morphogen signaling pathways modulates body axis formation in vertebrate embryos.

SUBMITTER: Takebayashi-Suzuki K

PROVIDER: S-EPMC7141137 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Intracellular Communication among Morphogen Signaling Pathways during Vertebrate Body Plan Formation.

Takebayashi-Suzuki Kimiko K Suzuki Atsushi A

Genes 20200324 3

During embryonic development in vertebrates, morphogens play an important role in cell fate determination and morphogenesis. Bone morphogenetic proteins (BMPs) belonging to the transforming growth factor-β (TGF-β) family control the dorsal-ventral (DV) patterning of embryos, whereas other morphogens such as fibroblast growth factor (FGF), Wnt family members, and retinoic acid (RA) regulate the formation of the anterior-posterior (AP) axis. Activation of morphogen signaling results in changes in ...[more]

PMID: 32213808

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Project description:BackgroundIntracellular signaling networks transmit signals from the cell membrane to the nucleus, via biochemical interactions. The goal is to regulate some target molecules, to properly control the cell function. Regulation of the target molecules occurs through the communication of several intermediate molecules that convey specific signals originated from the cell membrane to the specific target outputs.ResultsIn this study we propose to model intracellular signaling network as communication channels. We define the fundamental concepts of transmission error and signaling capacity for intracellular signaling networks, and devise proper methods for computing these parameters. The developed systematic methodology quantitatively shows how the signals that ligands provide upon binding can be lost in a pathological signaling network, due to the presence of some dysfunctional molecules. We show the lost signals result in message transmission error, i.e., incorrect regulation of target proteins at the network output. Furthermore, we show how dysfunctional molecules affect the signaling capacity of signaling networks and how the contributions of signaling molecules to the signaling capacity and signaling errors can be computed. The proposed approach can quantify the role of dysfunctional signaling molecules in the development of the pathology. We present experimental data on caspese3 and T cell signaling networks to demonstrate the biological relevance of the developed method and its predictions.ConclusionsThis study demonstrates how signal transmission and distortion in pathological signaling networks can be modeled and studied using the proposed methodology. The new methodology determines how much the functionality of molecules in a network can affect the signal transmission and regulation of the end molecules such as transcription factors. This can lead to the identification of novel critical molecules in signal transduction networks. Dysfunction of these critical molecules is likely to be associated with some complex human disorders. Such critical molecules have the potential to serve as proper targets for drug discovery.

Dataset Information

Intracellular Communication among Morphogen Signaling Pathways during Vertebrate Body Plan Formation.

Publications

Intracellular Communication among Morphogen Signaling Pathways during Vertebrate Body Plan Formation.

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