Biology subjects

Tanentzapf, G.

Publications and source records attributed to Tanentzapf, G..

7 recordsLinked to original sources

bioRxiv2025

Sex-specific differences in the regulation and function of cellular immunity in Drosophila

Sex differences in development and physiology are prevalent in animals. One physiological system with pronounced differences between the sexes is the immune system: the immune response in humans differs between sexes and results in differential susceptibility of males and females to autoimmune diseases, malignancies, and infectious diseases. However, much remains to be discovered about the mechanisms underlying these sex-based differences in immunity. Here, we use the Drosophila hematopoietic organ, the lymph gland, as a model to investigate sex differences in cellular immunity and determine the underlying mechanisms. We find that, in line with their smaller body size, males have smaller lymph glands than females that contain fewer blood progenitors and produce less immune cells. Single cell RNA-seq analysis of the lymph gland showed that they expressed that sex determination genes and identified substantial sex-specific differences in gene expression. By manipulating the sexual identity of different cell types in the lymph gland we show that a subset of these sex differences are controlled by organ-intrinsic mechanisms involving the hematopoietic niche. Importantly, we find a differential response between males and females to changes in insulin signaling, an important regulator of the immune response in the niche. Finally, we provide evidence for differences in the cellular immune response following infection between males and females. Overall, our results provide mechanistic insight into how sex differences in immunity are established. Authors SummaryOur paper deals with a fundamental question in biology, how does the sex of an organism influence its anatomy and physiology. In particular, we focus on sex-differences in immunity and stem cell function. We establish the Drosophila larva as a model for analysing sex-based differences in cellular immunity. Cellular immunity in Drosophila is based on the production of multiple types of mature immune cells from blood progenitors and takes place in the fly hematopoietic organ, the larval lymph gland. We find that sex controls the number of various cell types in the lymph gland (progenitors, and specific varieties of mature blood cells). These sex-differences vary by cell type and change depending on whether flies are raised under homeostatic or infection conditions. We provide insight into the mechanisms that mediate these sex differences, identifying a possible role for the hematopoietic niche and insulin signaling. Taken together our work not only serves as an initial characterization of baseline sex-differences in fly hematopoiesis and cellular immunity but also identifies important areas for future exploration.

immunology↗

bioRxiv2024

Detection of bacteria through taste receptors primes the cellular immune response

Animals use their sensory system to detect cues in their external environment, then communicate, process, and integrate these cues through the nervous system in order to elicit a specific response. Taste is an important cue used by animals to explore their external environment and can modulate various aspects of animal behavior and physiology. A major ongoing challenge for animals is to detect and respond to the presence of a variety of microbes in their environment. However, to date, the links between the sensory system and the response to pathogenic threats remain poorly understood. Here we show that Drosophila melanogaster larvae use their taste system to detect bacterial peptidoglycans in their environment and respond by modulating the activity of their cellular immune system. We show that specific PeptidoGlycan Receptor Proteins (PGRPs) act in aversive taste neurons, via a non-canonical Immune Deficiency (Imd) pathway. These PGRPs mediate signaling in taste neurons and control immune cells production in the larval hematopoietic organ, the lymph gland. Taste-mediated sensing of bacteria in larvae primes the immune system, and improves survival after infection in adult flies. These results demonstrate that sensory inputs such as taste play an important role in protecting animals from bacterial infection by providing a powerful adaptive response to potential pathogens. Overall, our findings add to the growing list of examples of crosstalk between the nervous and immune systems and provide novel and important mechanisms for linking them. One Sentence SummaryNajera Mazariegos et al. demonstrate that organisms can use taste to monitor their environment for potential immune challenges and activate their immune system if they detect bacteria.

immunology↗

bioRxiv2023

Formation of recurring transient Ca2+-based intercellular communities during Drosophila hematopoiesis

Tissue development occurs through a complex interplay between many individual cells. Yet, the fundamental question of how collective tissue behavior emerges from heterogeneous and noisy information processing and transfer at the single-cell level remains unknown. Here, we reveal that tissue scale signaling regulation can arise from local gap-junction mediated cell-cell signaling through the spatiotemporal establishment of an intermediate-scale of transient multicellular communication communities over the course of tissue development. We demonstrated this intermediate scale of emergent signaling using Ca2+ signaling in the intact, ex vivo cultured, live developing Drosophila hematopoietic organ, the Lymph Gland (LG). Recurrent activation of these transient signaling communities defined self-organized signaling "hotspots" that receive and transmit information to facilitate repetitive interactions with non-hotspot neighbors, transfer information across cells, and regulate the developmental progression of hotspots. Overall, this work bridges the scales between single-cell and emergent group behavior providing key mechanistic insight into how cells establish tissue-scale communication networks. Significance statementCells coordinate their internal state and behavior by exchanging information with other cells in their vicinity. These local interactions are integrated across space and time to enable synchronized function at the tissue scale. Using live microscopy imaging of the Drosophila Lymph Gland, and by applying computational analyses, we identified and characterized a new mode of cellular communication through self-organized recurring coordinated short-term activation at the intermediate scale of 3-8 cells, which we call "hotspots". We reveal that hotspots form over the course of tissue development, and are dependent on specific proteins, called gap-junctions, that enable communication between adjacent cells. Hotspots repeatedly transmit and retrieve information to and from their non-hotspot neighbors to spread information throughout the tissue to regulate and coordinate tissue function.

developmental biology↗

bioRxiv2022

An important role for triglyceride in regulating spermatogenesis

Drosophila is a powerful model to study how lipids affect spermatogenesis. Yet, the contribution of neutral lipids, a major lipid group which resides in organelles called lipid droplets (LD), to sperm development is largely unknown. Emerging evidence suggests LD are present in the testis and that loss of neutral lipid- and LD-associated genes causes subfertility; however, key regulators of testis neutral lipids and LD remain unclear. Here, we show LD are present in early-stage somatic and germline cells within the Drosophila testis. We identified a role for triglyceride lipase brummer (bmm) in regulating testis LD, and found that whole-body loss of bmm leads to defects in sperm development. Importantly, these represent cell-autonomous roles for bmm in regulating testis LD and spermatogenesis. Because lipidomic analysis of bmm mutants revealed excess triglyceride accumulation, and spermatogenic defects in bmm mutants were rescued by genetically blocking triglyceride synthesis, our data suggest that bmm-mediated regulation of triglyceride influences sperm development. This identifies triglyceride as an important neutral lipid that contributes to Drosophila sperm development, and reveals a key role for bmm in regulating testis triglyceride levels during spermatogenesis.

developmental biology↗

bioRxiv2022

Kinetics of blood cell differentiation during hematopoiesis revealed by quantitative long-term live imaging

Stem cells typically reside in a specialized physical and biochemical environment that facilitates regulation of their behavior. For this reason, stem cells are ideally studied in contexts that maintain this precisely constructed microenvironment while still allowing for live imaging. Here, we describe a long-term organ culture and imaging strategy for hematopoiesis in flies that takes advantage of powerful genetic and transgenic tools available in this system. We find that fly blood progenitors undergo symmetric cell divisions and that their division is both linked to cell size and is spatially oriented. Using quantitative imaging to simultaneously track markers for stemness and differentiation in progenitors, we identify two types of differentiation that exhibit distinct kinetics. Moreover, we find that infection-induced activation of hematopoiesis occurs through modulation of the kinetics of cell differentiation. Overall, our results show that even subtle shifts in proliferation and differentiation kinetics can have large and aggregate effects to transform blood progenitors from a quiescent to an activated state.

developmental biology↗

bioRxiv2021

Crosstalk with keratinocytes causes GNAQ oncogene specificity in melanoma

Different melanoma subtypes exhibit specific and non-overlapping sets of oncogene and tumor suppressor mutations, despite a common cell of origin in melanocytes. For example, activation of the Gq/11 signaling pathway is a characteristic initiating event in primary melanomas that arise in the dermis, uveal tract or central nervous system. It is rare in melanomas arising in the epidermis. Here, we present evidence that in the mouse, crosstalk with the epidermal microenvironment actively impairs the survival of melanocytes expressing the GNAQQ209L oncogene, providing a new model for oncogene specificity in cancer. The presence of epidermal cells inhibited cell division and fragmented dendrites of melanocytes expressing GNAQQ209L in culture, while they promoted the growth of normal melanocytes. Differential gene expression analysis of FACS sorted epidermal melanocytes showed that cells expressing GNAQQ209L exhibit an oxidative stress and apoptosis signature previously linked to vitiligo. Furthermore, PLCB4, the direct downstream effector of Gq/11 signaling, is frequently mutated in cutaneous melanoma alongside P53 and NF1. Our results suggest that a deficiency of PLCB4 promotes cutaneous melanomagenesis by reducing GNAQ driven signaling. Hence, our studies reveal the flip side of the GNAQ/PLCB4 signaling pathway, which was hitherto unsuspected. In the future, understanding how epidermal crosstalk restrains the GNAQQ209L oncogene could suggest novel melanoma therapies.

cancer biology↗

bioRxiv2017

Zebrafish yolk syncytial nuclei migrate along a dynamic microtubule network

In teleosts, the yolk syncytial layer is a multinucleate syncytium that functions as an extraembryonic signaling center to pattern the mesendoderm, coordinate morphogenesis and supply nutrients to the embryo. The zebrafish is an excellent system for studying this morphogenetically active tissue. The external yolk syncytial nuclei (e-YSN) undergo microtubule dependent epiboly movements that distribute the nuclei over the yolk. How e-YSN epiboly proceeds, and what role the yolk microtubule network plays is not understood but currently it is proposed that e-YSN are pulled vegetally as the microtubule network shortens from the vegetal pole. Data from our live imaging studies suggest that the yolk microtubule network is dismantled from the animal and vegetal regions and show that a region of stabilized microtubules forms before nuclear migration begins. e-YSN do not appear to be pulled vegetally but rather move along a dynamic microtubule network. We also show that overexpression of the KASH domain of Syne2a impairs e-YSN movement, implicating the LINC complex in e-YSN migration. This work provides new insights into the role of microtubules in morphogenesis of an extraembryonic tissue.\n\nSummary StatementAnalysis of yolk syncytial nuclear migration during zebrafish epiboly reveals that nuclei migrate along and largely beneath a dynamically yolk microtubule network.

developmental biology↗