Abstract

BackgroundIntercellular signaling via the Notch pathway regulates cell fate, patterning, differentiation and proliferation, and is essential for the proper development of bilaterians and cnidarians. To investigate the origins of the Notch pathway, we are studying its deployment in a representative of an early branching lineage, the poriferan Amphimedon queenslandica. The A. queenslandica genome encodes a single Notch receptor and five membrane-bound Delta ligands, as well as orthologs of many genes that enact and regulate canonical Notch signaling events in other animals.MethodsIn the present report we analyze the structure of the five A. queenslandica Deltas using bioinformatic methods, and characterize their developmental expression via whole mount in situ hybridization and histological staining.ResultsSequence analysis of the A. queenslandica Delta ligands highlights the conservation of their extracellular domains. This contrasts with the divergence of their intracellular regions, each of which is predicted to bear a unique repertoire of protein interaction motifs. In keeping with this diversity, these ligands are expressed differentially and dynamically throughout A. queenslandica embryogenesis, both in cell type specific patterns and broader regional domains. Notably, this expression coincides with the development of the photosensitive larval pigment ring, the non-ciliated cuboidal cells located at the anterior pole of the larva, and the intraepithelial flask cells and globular cells that are presumed to have sensory and/or secretory roles.ConclusionsBased on the dynamic and complex patterns of expression of these Delta ligands and the Notch receptor, we propose that the Notch signaling pathway is involved in regulating the development of diverse cell types in A. queenslandica. From these observations we infer that Notch signaling is a conserved feature of metazoan development, ancestrally contributing to cell determination, patterning and differentiation processes.

Highlights

  • Intercellular signaling via the Notch pathway regulates cell fate, patterning, differentiation and proliferation, and is essential for the proper development of bilaterians and cnidarians

  • Of the major developmental signaling pathways, comparative studies have revealed that core components of the Wnt, Notch, transforming growth factor β (TGFβ) and receptor tyrosine kinase (RTK) pathways are encoded in the genomes

  • The Notch intracellular domain (NICD) translocates to the nucleus of the receiving cell, where it binds to the CBF1/Suppressor of hairless/Lag1 (CSL) repressor complex and elicits a change in the transcriptional activity of the cell

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Summary

Introduction

Intercellular signaling via the Notch pathway regulates cell fate, patterning, differentiation and proliferation, and is essential for the proper development of bilaterians and cnidarians. The A. queenslandica genome encodes a single Notch receptor and five membrane-bound Delta ligands, as well as orthologs of many genes that enact and regulate canonical Notch signaling events in other animals. Notch signaling events act to regulate the responsiveness of individual cells, or cell populations, to the developmental instructions they encounter [6]. In this capacity, Notch signaling has been shown to direct cell specification, differentiation and proliferation, delineate boundaries between developmental fields, and regulate cell migration and apoptotic events (reviewed in [3,7])

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