Biology

Dr. Kalpana Makhijani
University of California San Fransisco

The Peripheral Nervous System (PNS) has been recognized as a major regulator in the development and homeostasis of many organ systems and cell microenvironments (niches). However, how the sensory nervous system, which innervates all organ systems including hematopoietic tissues, regulates blood cell behaviors and contributes to disease have not been addressed. To address this question at the cellular and molecular level, I and my colleagues at Dr. Katja Brückner’s laboratory at University of California San Francisco, developed a simple invertebrate model for PNS support and regulation of hematopoiesis, using the optically transparent larva of the genetically tractable model organism Drosophila melanogaster. We showed that, blood cells (hemocytes) colonize segmentally repeated hematopoietic pockets of the larval body wall, where they develop in direct physical contact with sensory PNS clusters. Hemocytes functionally rely on the PNS for homing and trophic survival, and are induced to proliferate in these microenvironments (Makhijani et al 2011, 2012). We also found that the larval hemocytes, 95% of which are plasmatocytes performing phagocytic functions, self renew in a progenitor independent manner much like the tissue macrophages that colonize various vertebrate organs during embryonic development (Makhijani et al 2011, 2012).

Focusing on identifying the molecular mechanism by which PNS regulates hematopoiesis, we show that the elusive PNS signal is a Tgf-β related protein, Activin β that regulates the proliferation and adhesion of larval hemocytes (Makhijani et al., submitted manuscript). Manipulating neuronal activity affects normal hematopoiesis and Activin expression thus suggesting that PNS acts as an interface through which sensory stimuli regulate blood cell responses. These studies are significant for understanding the microenvironment signals required for maintenance of the evolutionarily related self-renewing tissue macrophages in vertebrates, which are important in providing local immunity of a tissue or organ system and the regulation of blood cell responses in response to external environment.