Neuroglian regulatesDrosophilaintestinal stem cell proliferation through enhanced signaling via the Epidermal Growth Factor Receptor

Abstract

SummaryThe Drosophila melanogaster intestine is an excellent system for elucidating mechanisms regulating stem cell behavior under homeostatic conditions or in response to injury, stress, or ageing. Here we show that the septate junction (SJ) protein Neuroglian (Nrg) is expressed in intestinal stem cells (ISCs) and daughter enteroblasts (EBs) within the fly midgut, the equivalent of the mammalian small intestine. Although Nrg localizes to the plasma membrane, SJs are not present between ISC/EBs, suggesting Nrg plays a different role in this tissue. Generation of ISCs homozygous for a null allele of Nrg revealed that Nrg is required for ISC proliferation in young flies, and depletion of Nrg from ISCs/EBs was able to suppress the increase in ISC proliferation with age. Conversely, overexpression of Nrg in ISC/EBs was sufficient to drive ISC proliferation, leading to an increase in cells expressing ISC/EB markers. In addition, we observed an increase in EGFR activation. Genetic epistasis experiments revealed that Nrg acts upstream of EGFR in the midgut to regulate ISC proliferation. As Nrg function is highly conserved in mammalian systems, our work characterizing the role of Nrg in the intestine has implications for the etiology and treatment of intestinal disorders due to altered ISC behavior.

Cooperation between bacteriocytes and endosymbionts drives function and development of symbiotic cells in mussel holobionts

“…4B) in a manner similar to that observed in fish gills 36 . In addition to the previously identified markers gene, our scRNA-seq and ST-seq data further identified massive cell cycle-, proliferation-, and differentiation-related genes in PEBZCs (cluster 2/6) and DEPCs (cluster 0) [including several markers of stem cells such as DEK 37,38 , Serine/arginine-rich splicing factor 1 39 , protein hedgehog 40,41 , nesprin-1 42 , protein crumbs-like 2 43,44 , repulsive guidance molecule A 45 , G1/S-specific cyclin-E gene 46,47 , calcium/calmodulin-dependent protein kinase type II 48,49 , prospero homeobox protein 1 50 , Neuroglian 51 , SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1 52,53 , bone morphogenic protein type 2 receptor 54 , and protein strawberry notch homolog 1 55 ] (Supplementary Table 2). Using an expression atlas of stem cells and bacteriocyte lineages, we then characterized the bacteriocyte development trajectory using three different models: pseudo-time analysis by Monocle (Fig.…”