Origin and evolution of the Notch signalling pathway: an overview from eukaryotic genomes

Abstract

Background: Of the 20 or so signal transduction pathways that orchestrate cell-cell interactions in metazoans, seven are involved during development. One of these is the Notch signalling pathway which regulates cellular identity, proliferation, differentiation and apoptosis via the developmental processes of lateral inhibition and boundary induction. In light of this essential role played in metazoan development, we surveyed a wide range of eukaryotic genomes to determine the origin and evolution of the components and auxiliary factors that compose and modulate this pathway.

Phylogenetic evidence for the modular evolution of metazoan signalling pathways

“…Specifically, many of the enzymes associated with this pathway (e.g. ubiquitin ligases and ADAM-type proteases) were present before the origin of Metazoa, suggesting Notch/Delta signalling may have evolved by co-option of an existing intracellular cascade [100]. Notch/Delta signalling functions primarily in promoting differential cell identity in subpopulations of adjacent cells.…”

“…Indeed, the hedgehog pathway is an excellent example of this-hedge and hog domains are present in the lineages leading up to the Metazoa but the complete hedgehog gene did not arise until the stem lineage giving rise to Cnidaria þ Bilateria [109]. Likewise, there is very good evidence for the piecewise assembly of genes in the JAK/STAT pathway [137], Notch/ Delta pathway [100] and the evolution of the ECM [142]. Another striking pattern to be drawn from this summary is the timing of evolution of the components of each pathway.…”

Notch signaling in the brain: In good and bad times

“…The Notch pathway is highly conserved in metazoans (Gazave et al, 2009). It occurs early on in development, when cell-tocell contact determines morphogenesis .…”

“…On the other hand, in Drosophila, Delta1 seems to be the relevant Notch ligand from development to the mature brain (Lieber et al, 2011;Muskavitch, 1994). It is not clear why ligand functions and topology are not conserved, but the separation of Delta and Jagged expression in different metazoan species has recently been reported (Gazave et al, 2009).…”

Le génome de l’épongeAmphimedon queenslandicanous aide à reconstruire notre ancêtre précambrien

“…Cependant, la voie Hedgehog semble avoir été limitée chez cet ancêtre à la signalisation entre cellules voisines (comme la voie Notch) et non sur de plus longues distances comme c'est le cas chez les bilatériens actuels [10]. Comme pour les facteurs de transcription, il y a ensuite eu une diversification des cascades dans la lignée de l'ancêtre eumétazoaire, particulièrement au niveau des ligands, des récepteurs et des répresseurs, plutôt que pendant la troisième période entre les ancêtres eumétazoaire et bilatérien [2,[11][12][13]. En effet, l'ancêtre euméta-zoaire possédait déjà 12 des 13 gènes Wnt qui sont partagés par les bilaté-riens, alors que l'éponge Amphimedon n'en a que trois.…”