The Notch signaling pathway in the cnidarian Hydra

Abstract

Many of the major pathways that govern early development in higher animals have been identified in cnidarians, including the Wnt, TGFbeta and tyrosine kinase signaling pathways. We show here that Notch signaling is also conserved in these early metazoans. We describe the Hydra Notch receptor (HvNotch) and provide evidence for the conservation of the Notch signaling mode via regulated intramembrane proteolysis. We observed that nuclear translocation of the Notch intracellular domain (NID) was inhibited by the synthetic gamma-secretase inhibitor DAPT. Moreover, DAPT treatment of hydra polyps caused distinct differentiation defects in their interstitial stem cell lineage. Nerve cell differentiation proceeded normally but post-mitotic nematocyte differentiation was dramatically reduced. Early female germ cell differentiation was inhibited before exit from mitosis. From these results we conclude that gamma-secretase activity and presumably Notch signaling are required to control differentiation events in the interstitial cell lineage of Hydra.

Genomic insights into the evolutionary origin of Myxozoa within Cnidaria

“…The two myxozoans and P. hydriforme were also found to have key elements of the Notch-signaling pathway, and M. cerebralis possessed some elements of the TGFβ pathway (Table 4 and Dataset S3). Notch is reported to have an important role in differentiation of stem-cell lineages (50), whereas TGFβ appears to play a more general role in cell signaling (51).…”

Phylogenetic evidence for the modular evolution of metazoan signalling pathways

“…Beyond the ligand (Delta) and receptor (Notch), the proteases that process the Notch preprotein (furin, O-fut and fringe) and liberate the intracellular domain from the extracellular domain (ADAM-type metalloproteases and the g-secretase complex) are critically important for effective signalling. Outside of Bilateria, Notch homologues have been found in cnidarians [27,99], placozoans [11,15], sponges [17] and ctenophores [11,13]. Notch-like proteins have also been described from the choanoflagellate Monosiga brevicollis and the filasterean Capsaspora owczarzaki, though these proteins lack key functional domains including the Delta interaction domain (DSL) in the former and the epidermal growth factor (EGF) domains in both taxa [26].…”

“…Notch/Delta signalling pathways are known to be functional in cnidarians and bilaterians but the roles of these pathways may be quite different in these two lineages. Pharmacological studies using the g-secretase inhibitor DAPT have identified a role for Notch/Delta signalling in neural specification across cnidarians [99,104,105], but knockdown experiments in the sea anemone N. vectensis suggest that cnidarians use the non-canonical Notch pathway, independent of the hairy/enhancer of split (HES) transcription factors, in this process [106]. Curiously, cnidarians have orthologues of HES genes (indeed, HES genes are found throughout Metazoa), suggesting that the canonical Notch/HES signalling pathway may be used in a context other than neural specification in non-bilaterian metazoans.…”

The Hydra model: disclosing an apoptosis-driven generator of Wnt-based regeneration

“…These studies identified the differentiation pathways of most cell types in homeostatic and regenerative conditions. In addition, the molecular work performed over the past 20 years has started to dissect the genetic pathways at work during budding, regeneration and reaggregation as the canonical Wnt pathway for maintaining and re-establishing apical organizer activity [33][34][35][36][37][38][39] , the non-canonical Wnt pathway for cellular evagination processes 38 , the MAPK-CREB pathway for triggering head regeneration 46 , the BMP/chordin pathway for axis patterning 47,48 , the FGF pathway for bud detachment 49 , the Notch pathway for differentiating some interstitial cell lineages 50 .…”