Intracellular trafficking of Notch orchestrates temporal dynamics of Notch activity in the fly brain

While Delta non-autonomously activates Notch in neighboring cells, it autonomously inactivates Notch through cis-inhibition, the molecular mechanism and biological roles of which remain elusive. The wave of differentiation in the Drosophila brain, the ‘proneural wave’, is an excellent model for studying Notch signaling in vivo. Here, we show that strong nonlinearity in cis-inhibition reproduces the second peak of Notch activity behind the proneural wave in silico. Based on this, we demonstrate that Delta expression induces a quick degradation of Notch in late endosomes and the formation of the twin peaks of Notch activity in vivo. Indeed, the amount of Notch is upregulated and the twin peaks are fused forming a single peak when the function of Delta or late endosomes is compromised. Additionally, we show that the second Notch peak behind the wavefront controls neurogenesis. Thus, intracellular trafficking of Notch orchestrates the temporal dynamics of Notch activity and the temporal patterning of neurogenesis.

Late Cambrian ptychaspidid trilobites from western Utah: implications for trilobite systematics and biostratigraphy

The Notch Peak Formation (Late Cambrian, Sunwaptan) of western Utah yields diverse silicified trilobite faunas that provide new information on the anatomy of many taxa. The family Ptychaspididae Raymond, 1924, is represented by species of Keithiella Rasetti, 1944; Idiomesus Raymond, 1924; Euptychaspis Ulrich in Bridge, 1931; and Macronoda Lochman, 1964. At least four species are new, of which E. lawsonensis and M. notchpeakensis are named formally. Much previous work on Late Cambrian trilobites has emphasized biostratigraphic utility and the recognition of geographically widespread species. Data from new silicified collections indicate that this approach is difficult to justify because many putative ‘index species’ actually represent a plexus of closely related species whose biostratigraphic significance has yet to be determined. One such plexus is represented by E. kirki Kobayashi, 1935, whose previously reported occurrences in Texas, Oklahoma, Utah, Nevada and northern Canada record at least four distinct species. Similarly, Macronoda can now be shown to consist of at least five late Sunwaptan species in south-central and western North America.