Abstract

Blood progenitors within the lymph gland, a larval organ that supports hematopoiesis in Drosophila melanogaster, are maintained by integrating signals emanating from niche-like cells and those from differentiating blood cells. We term the signal from differentiating cells the 'equilibrium signal' in order to distinguish it from the 'niche signal'. Earlier we showed that equilibrium signaling utilizes Pvr (the Drosophila PDGF/VEGF receptor), STAT92E, and adenosine deaminase-related growth factor A (ADGF-A) (Mondal et al., 2011). Little is known about how this signal initiates during hematopoietic development. To identify new genes involved in lymph gland blood progenitor maintenance, particularly those involved in equilibrium signaling, we performed a genetic screen that identified bip1 (bric à brac interacting protein 1) and Nucleoporin 98 (Nup98) as additional regulators of the equilibrium signal. We show that the products of these genes along with the Bip1-interacting protein RpS8 (Ribosomal protein S8) are required for the proper expression of Pvr.

Highlights

  • Blood cell differentiation in Drosophila is regulated in multiple hematopoietic environments, which include the head mesoderm of the embryo (Tepass et al, 1994; Lebestky et al, 2000; Milchanowski et al, 2004), the specialized, tissue-associated microenvironments of the larval periphery (Markus et al, 2009; Makhijani et al, 2011), and the larval lymph gland, an organ dedicated to the development of blood cells that normally contribute to the pupal and adult stages (Rizki, 1978; Shrestha and Gateff, 1982; Lanot et al, 2001; Jung et al, 2005)

  • These blood progenitors readily proliferate during the early growth phases of lymph gland development, which is followed by a period in which many of these cells slow their rate of division and are maintained without differentiation in a region termed the medullary zone (MZ, Figure 1) (Jung et al, 2005; Mandal et al, 2007)

  • Using the pan-lymph gland HHLT-gal4 driver, we identified 21 RNAi lines that cause a loss of progenitor cells in the primary lobes at late stages of lymph gland development

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Summary

Introduction

Blood cell differentiation in Drosophila is regulated in multiple hematopoietic environments, which include the head mesoderm of the embryo (Tepass et al, 1994; Lebestky et al, 2000; Milchanowski et al, 2004), the specialized, tissue-associated microenvironments of the larval periphery (e.g, body wall hematopoietic pockets) (Markus et al, 2009; Makhijani et al, 2011), and the larval lymph gland, an organ dedicated to the development of blood cells that normally contribute to the pupal and adult stages (Rizki, 1978; Shrestha and Gateff, 1982; Lanot et al, 2001; Jung et al, 2005). These data support a model in which Bip1 functions along with RpS8 in a protein complex within differentiating cells to maintain multipotent lymph gland progenitors at later stages of development, consistent with a potential function in the equilibrium signaling pathway. These results place bip1 function genetically upstream of Pvr and other equilibrium signaling components in lymph gland progenitor maintenance by differentiating cells.

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