Lesson 8.6 anyway you slice it answers driver#

The orthologue of Lz in mammals is RUNX1, with broad hematopoietic function at many developmental stages, and RUNX1 is often dysregulated in acute myeloid leukemias ( de Bruijn and Speck, 2004 Ito, 2004). The transcription factor Lozenge (Lz) cooperates with Notch signaling to express a number of target genes (such as hindsight/ pebbled) to specify CCs ( Lebestky et al., 2000 Duvic et al., 2002), whereas the Sima (vertebrate HIF-1α) protein is required for their maintenance ( Mukherjee et al., 2011). CCs are necessary for melanization, blood clot formation, immunity against bacterial infections, and to help mitigate hypoxic stress ( Rämet et al., 2002 Galko and Krasnow, 2004 Binggeli et al., 2014 Dudzic et al., 2015 Cho et al., 2018). A minor (2–5%), but important class is represented by crystal cells (CCs) named for their crystalline inclusions of the pro-phenoloxidase enzymes, PPO1 and PPO2. PLs function in the engulfment of microbes and apoptotic cells, and they produce extracellular matrix proteins ( Fessler and Fessler, 1989 Tepass et al., 1994 Franc et al., 1996). The most predominant class of blood cells, the plasmatocytes (PLs 95% of all hemocytes), share a monophyletic relationship with vertebrate macrophages. Accordingly, Drosophila blood cells are all similar in function to cells of the vertebrate myeloid lineage. Invertebrates predate the evolution of the lymphoid system for adaptive immunity. A narrow band of cells that are double positive for dome MESO and Hml Δ occupy the edge abutting these two zones in the early third instar ( Sinenko et al., 2009), and is referred to as the intermediate zone (IZ), which contains intermediate progenitors (IPs) ( Krzemien et al., 2010). Differentiating cells form the cortical zone (CZ), expressing Hemolectin ( Hml), Peroxidasin ( Pxn), lozenge ( lz), and other differentiating cell markers ( Jung et al., 2005). The PSC signals progenitors that belong to the medullary zone (MZ) and are marked by dome MESO and Tep4 ( Jung et al., 2005 Irving et al., 2005). The PSC (Posterior Signaling Center) is marked by expression of Antp ( Mandal et al., 2007) and knot/ collier ( kn/ col) ( Crozatier et al., 2004). Past work has identified specific functional zones. This study entirely concentrates on the primary/anterior lobes of the lymph gland, which display the highest hematopoietic activity during normal larval development. The only time the lymph gland provides blood cells to the circulating larval hemolymph is if the larva faces a stress or immune challenge. Hematopoietic function for the larva itself is largely provided by a separate set of sessile or circulating blood cells outside of the lymph gland (reviewed in Letourneau et al., 2016). The Drosophila lymph gland is the major hematopoietic organ that develops during the larval stages for the purpose of providing blood cells during later pupal/adult periods (reviewed in Banerjee et al., 2019).

Increasingly, this view is gaining support in mammalian hematopoiesis. Broadly, we find that prior to making a fate choice, a progenitor selects between alternative, biologically relevant, transitory states allowing smooth transitions reflective of combinatorial expressions rather than stepwise binary decisions. Mechanistically, the Musashi-regulated protein Numb facilitates Sima-dependent non-canonical, and inhibits canonical, Notch signaling.

Lesson 8.6 anyway you slice it answers driver#

We highlight metabolism as a driver of development, show that graded Pointed expression allows distinct roles in successive developmental steps, and that mature crystal cells specifically express an alternate isoform of Hypoxia-inducible factor (Hif/Sima). This provides functional insights into key developmental processes and signaling pathways.

Using a combination of bulk RNA-Seq of FACS-sorted cells, single-cell RNA-Seq, and genetic dissection, we identify new blood cell subpopulations along a developmental trajectory with multiple paths to mature cell types. Mechanistic studies of Drosophila lymph gland hematopoiesis are limited by the availability of cell-type-specific markers.