Notch Signaling - Where Did it Come from? (four papers)

1. Notchless, a component of the pathway, is present in plant and yeast -

From the Notch Signaling Pathway to Ribosome Biogenesis

Nearly 240 WD repeat proteins have been identified from the Arabidopsis genome. Among these, some well characterized WDR proteins were shown to regulate various developmental processes in plants.1 We have recently isolated in Solanum chacoense a homolog of the Drosophila NOTCHLESS gene. In Drosophila, NOTCHLESS regulates the activity of the Notch signaling pathway through a direct interaction with the intracellular domain of the Notch receptor. Although the Notch signaling pathway does not exist in yease and plants, the NLE gene is conserved in animals, plants and yeast. Furthermore, functional conservation was suggested by expression of the plant NLE gene in Drosophila. In plants, underexpression of the plant NLE gene altered numerous developmental processes including seed development, and resulted in reduced aerial organ size and organ numbers, in delayed flowering, and in an increased stomatal index. Surprisingly, the link between these pleiotropic phenotypes is the recently discovered of the involvement of NLE in ribosome biogenesis, emphasizing its role in proper cellular growth and proliferation during plant development.

2. Phylogeny analysis -

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


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.


We searched for 22 components of the Notch pathway in 35 different species that represent 8 major clades of eukaryotes, performed phylogenetic analyses and compared the domain compositions of the two fundamental molecules: the receptor Notch and its ligands Delta/Jagged. We confirm that a Notch pathway, with true receptors and ligands is specific to the Metazoa. This study also sheds light on the deep ancestry of a number of genes involved in this pathway, while other members are revealed to have a more recent origin. The origin of several components can be accounted for by the shuffling of pre- existing protein domains, or via lateral gene transfer. In addition, certain domains have appeared de novo more recently, and can be considered metazoan synapomorphies.


The Notch signalling pathway emerged in Metazoa via a diversity of molecular mechanisms, incorporating both novel and ancient protein domains during eukaryote evolution. Thus, a functional Notch signalling pathway was probably present in Urmetazoa.

3. Conceptual paper from 2006 -

Evolutionary Origins of Notch Signaling in Early Development

Notch signaling is known to play key roles in early embryonic development and in the specification or patterning of germ layers in several lower organisms. Thus it is surprising that the removal of maternal and zygotic protein O-fucosyltransferase 1 (Pofut1), an essential component of the canonical Notch signaling pathway, does not affect early embryogenesis in the mouse.1 Mouse embryos lacking Pofut1 develop normally through blastogenesis to E8.0 when all three germ layers have formed.1 Here we summarize roles for Notch signaling in early embryonic development of several species, and discuss the potential evolutionary origins of these roles. We propose that Notch signaling might have first been used in the common ancestor of the metazoa for certain advanced developmental processes such as segmentation, and only later in evolution been coopted for use at early stages of embryogenesis in some organisms.

4. Conceptual paper from 2011 -

Notch signaling: simplicity in design, versatility in function

Notch signaling is evolutionarily conserved and operates in many cell types and at various stages during development. Notch signaling must therefore be able to generate appropriate signaling outputs in a variety of cellular contexts. This need for versatility in Notch signaling is in apparent contrast to the simple molecular design of the core pathway. Here, we review recent studies in nematodes, Drosophila and vertebrate systems that begin to shed light on how versatility in Notch signaling output is generated, how signal strength is modulated, and how cross-talk between the Notch pathway and other intracellular signaling systems, such as the Wnt, hypoxia and BMP pathways, contributes to signaling diversity.

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Written by M. //