Notch controls arterialization by regulating the cell cycle and not differentiation

Arteries are thought to be formed by the induction of a highly conserved arterial genetic program in a subset of vessels experiencing an increase in pulsatile and oxygenated blood flow. Both VEGF and Notch signalling have been shown to be essential for the initial steps of arterial specification. Here, we combined inducible genetic mosaics and transcriptomics to modulate and understand the function of these signalling pathways on cell proliferation, arterial-venous differentiation and mobilization. We observed that endothelial cells with high VEGF or Notch signalling are not genetically pre-determined and can form both arteries and veins. Importantly, cells completely lacking the Notch-Rbpj transcriptional activator complex can form arteries when the Myc-dependent metabolic and cell-cycle activity is suppressed. Thus, arterial development does not require the induction of a Notch-dependent arterial differentiation program, but rather the timely suppression of the endothelial metabolism and cell-cycle, a process preceding arterial mobilization and complete differentiation.

Extensive hybridization between pig and human Ascaris identifies a highly interbred species complex infecting humans

Human ascariasis is a major neglected tropical disease caused by the nematode Ascaris lumbricoides. We report a 296 megabase (Mb) reference quality genome comprised of 17902 protein-coding genes derived from a single, representative Ascaris worm collected from 60 human hosts in Kenyan villages where pig husbandry is rare. Notably, the majority of human isolates (63/68) possessed mitochondrial genomes that clustered closer to the pig parasite Ascaris suum than to A. lumbricoides. Comparative phylogenomic analyses identified over 11 million nuclear-encoded SNPs but just two distinct genetic types that had recombined across the genomes analysed. The nuclear genomes had extensive heterozygosity and all samples existed as genetic mosaics with either A. suum-like or A. lumbricoides-like inheritance patterns supporting a highly interbred Ascaris species genetic complex. As no barriers appear to exist for anthroponotic transmission of these “hybrid” worms, a one-health approach to control the spread of human ascariasis will be necessary.

Genital disc growth in Drosophila

Prior to completion, apoptosis causes the secretion of different signals, including proliferative signals. Signaling associated with death was discovered in Drosophila and mostly characterized by the induction of experimental death. Thus, less is known about physiological death. Here, we analyzed physiological death in the genital disc, a structure with bilateral symmetry, in different growth scenarios. To this end, we prevented or promoted death in regions or in genetic mosaics. We observed that physiological death in the genital disc was associated with proliferative signals and that both processes were JNK-dependent. The proliferative signals promoted growth in the genitalia primordia but not in the analia. Due to the proliferative signaling, the prevention of death that produced undead cells provoked asymmetric growth, high variability in proliferation, and size reduction. Death can occur in the absence of JNK but without signaling. JNK is fundamental for growth and death associated with signaling.