Genetics and the environment in animal development and homeostasis
Developmental biology research has focused on the role of genetic programs, and the contribution of physiological factors, such as nutrition and metabolism, and microbiota and pathogens. However, one of the outstanding questions in developmental biology is how sensory inputs from the environment regulate animal development and homeostasis, resulting in tissue adaptation and increased animal fitness. The Brückner laboratory investigates the molecular mechanisms by which sensory inputs from the environment regulate self-renewing cell populations, through local neuronal connections.
Peripheral neurons as hematopoietic microenvironment
The Brückner laboratory studies a simple Drosophila melanogaster model of niche support by the peripheral nervous system (PNS), focusing on the hematopoietic system as a target tissue. The model takes advantage of hematopoietic pockets (HPs) present in the body wall of the optically transparent Drosophila larva. In the HPs, blood cells (hemocytes) reside in direct physical contact with segmentally repeated clusters of sensory PNS neurons (Makhijani et al. Development 2011; Makhijani et al. Fly 2012;Gold and Brückner Exp Hematology 2014). Functionally, hemocytes rely on the PNS for their localization and trophic survival, and they show increased proliferation in these hematopoietic microenvironments (Makhijani et al. Development 2011). Our studies have identified a PNS neuron-produced regulator of hemocyte adhesion and localization, demonstrating that factors from the PNS determine blood cell signaling and biological responses (Makhijani et al. submitted). Current research examines the contribution of other neuron-produced factors on blood cell induction and biology.The anatomical proximity of hemocytes with sensory neurons within HPs suggests that blood cell responses might be environmentally modulated by sensory stimuli. Indeed, we have found that transient silencing of PNS neuronal activity abolishes normal hemocyte behaviors (Makhijani et al. submitted). Currently, we are studying the molecular mechanisms by which natural sensory stimuli regulate the larval blood cell pool. To complement our studies in the larva, we are also investigating how modulation of the larval blood cell pool by sensory activation increases the fitness of the adult animal. Drosophila larval hemocytes show plasticity to differentiate into other blood cell types, and share similarities with the vertebrate lineage of self-renewing tissue macrophages, whose local regulation remains enigmatic in vertebrate systems.
Hematopoiesis in the Drosophila model
The early waves of hematopoiesis in Drosophila have been well described (embryonic, larval and lymph gland hematopoiesis, see Makhijani and Brückner Fly 2012, and Gold and Brückner Exp Hematol 2014), but little is known about the blood cell system at later stages and in the adult animal. The Brückner laboratory investigates blood cells in the adult and their relationship to the nervous system and other tissues.
Crosstalk in cell signalling
The Brückner laboratory is interested in how signaling pathways and their cross talk underlie a variety of cell behaviors, including cell survival, proliferation, and epithelial plasticity responses, which play important roles during development and pathological conditions such as fibrosis and cancer metastasis. Taking advantage of the evolutionary conservation and low genetic redundancy of Drosophila, we use various Drosophila cell culture systems to perform cell-based RNAi and study cellular responses. We utilize classical cell lines, such as Kc (Brückner et al. Dev Cell 2004), but we have also developed unique cell lines including the epithelial line KaBrü1D1, which is Dpp/BMP responsive. Our studies comprise cell biological, biochemical and genomic approaches, and we use Drosophila in vivo systems of blood cell development and epithelial plasticity during thorax closure to verify molecular findings.