Article

The peripheral nervous system supports blood cell homing and survival in the Drosophila larva

Department of Cell and Tissue Biology, University of California-San Francisco, 35 Medical Center Way, San Francisco, CA 94143-0669, USA.
Development (Impact Factor: 6.27). 11/2011; 138(24):5379-91. DOI: 10.1242/dev.067322
Source: PubMed

ABSTRACT Interactions of hematopoietic cells with their microenvironment control blood cell colonization, homing and hematopoiesis. Here, we introduce larval hematopoiesis as the first Drosophila model for hematopoietic colonization and the role of the peripheral nervous system (PNS) as a microenvironment in hematopoiesis. The Drosophila larval hematopoietic system is founded by differentiated hemocytes of the embryo, which colonize segmentally repeated epidermal-muscular pockets and proliferate in these locations. Importantly, we show that these resident hemocytes tightly colocalize with peripheral neurons and we demonstrate that larval hemocytes depend on the PNS as an attractive and trophic microenvironment. atonal (ato) mutant or genetically ablated larvae, which are deficient for subsets of peripheral neurons, show a progressive apoptotic decline in hemocytes and an incomplete resident hemocyte pattern, whereas supernumerary peripheral neurons induced by ectopic expression of the proneural gene scute (sc) misdirect hemocytes to these ectopic locations. This PNS-hematopoietic connection in Drosophila parallels the emerging role of the PNS in hematopoiesis and immune functions in vertebrates, and provides the basis for the systematic genetic dissection of the PNS-hematopoietic axis in the future.

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    • "Similar to vertebrates, 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). Understanding how blood cell development is regulated in the lymph gland is the primary goal underlying the work presented here. "
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    • "Communication between the nervous system and the peripheral immune system is becoming more and more evident in mammals as well as in invertebrates, and it is now recognized that the immune and nervous systems rely on constant interaction to maintain homeostasis (Evans et al., 2010; Ransohoff and Engelhardt, 2012; An et al., 2014). For example, nonmyelinating Schwann cells associated with the autonomic innervation of bone marrow contribute to the maintenance of the hematopoietic stem cell pool in mice (Yamazaki et al., 2011), and the peripheral nervous system provides a microenvironment important for ''homing'' of hematopoietic cells and regulating their survival and development in Drosophila larvae (Makhijani et al., 2011). The studies presented in this article reveal a similarly intimate relationship between the immune and nervous systems in freshwater crayfish (Procambarus clarkii and Pacifastacus leniusculus), where the production of neurons continues throughout the organisms' lives (for review, see Beltz et al., 2011; Benton et al., 2013). "
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