Biology subjects

Halberg, K. V.

Publications and source records attributed to Halberg, K. V..

4 recordsLinked to original sources

bioRxiv2024

Something old, something new: the origins of an unusual renal cell underpinning a beetle water-conserving mechanism

Tenebrionid beetles have been highly successful in colonising environments where water is scarce, underpinned by their unique osmoregulatory adaptations. These include a cryptonephridial arrangement of their organs, in which part of their renal/Malpighian tubules are bound to the surface of the rectum. This allows them to generate a steep osmotic gradient to draw water from within the rectum and return it to the body. Within the cryptonephridial tubules a seemingly novel cell type, the leptophragmata, is considered to play a key role in transporting potassium chloride to generate this osmotic gradient. Nothing was known about the developmental mechanisms or evolution of these unusual renal cells. Here we investigate the mechanisms underpinning development of the leptophragmata in the red flour beetle, Tribolium castaneum. We find that leptophragmata express and require a teashirt/tiptop transcription factor gene, as do the secondary renal cells of Drosophila melanogaster which lack a cryptonephridial arrangement. We also find an additional transcription factor, Dachshund, is required to establish leptophragmata identity and to distinguish them from the secondary cells in Triboliums non-cryptonephridial region of renal tubule. Dachshund is also expressed in a sub-population of secondary cells in Drosophila. So leptophragmata, which are unique to the beetle lineage, appear to have originated from a specific renal cell type present ancestrally, and specified by a conserved repertoire of transcription factors. SignificanceBeetles are a highly successful insect group and represent a quarter of all known animal species. Their digestive/renal systems have undergone major evolutionary change compared to other insects, likely contributing to their success. A dramatic example is the cryptonephridial complex, an evolutionary innovation of the gut and renal system which integrate as a powerful water-conservation system; an adaptation for survival in arid conditions. An unusual renal cell type--the leptophragmata--underpin the functions of the complex, but their developmental and evolutionary origins are unknown. Here we reveal the developmental mechanism that establish leptophragmata identity and, by studying a species lacking a cryptonephridial complex, shed light on their evolutionary origin. More broadly, the work illuminates the evolution of novel cell types.

developmental biology↗

bioRxiv2023

A neuronal relay mediates muscle-adipose communication that drives systemic metabolic adaptation to high-sugar diets

Obesity leads to impaired insulin signaling and tissue sensitivity, which drive the onset of type 2 diabetes. Insulin resistance leads to a reduction in cellular glucose uptake, resulting in elevated blood glucose levels, which consequently cause {beta}-cell dysfunction and development of diabetes. Although improving insulin signaling is a key target for restoring whole-body glucose homeostasis and reversing diabetes, the multi-organ mechanisms that regulate insulin signaling and tissue sensitivity are poorly defined. We screened the secretome and receptome in Drosophila to identify the underlying interorgan hormonal crosstalk affecting diet-induced insulin resistance and obesity. We identified complex interplay between muscle, neuronal, and fat tissues, mediated by the conserved BMP and LGR signaling pathways, which augments insulin signaling and improves dietary sugar tolerance. We found that muscle-derived BMP signaling is induced by sugar and governs neuronal Bursicon signaling. Acting through its LGR-family receptor, Bursicon both enhances insulin secretion and improves insulin sensitivity in adipose tissue, thereby preventing sugar-induced hyperglycemia. Inhibition of Bursicon-LGR signaling in adipose tissue exacerbates sugar-induced insulin resistance, and we discovered that this condition could be alleviated by suppressing NF-{kappa}B signaling. Our findings identify a muscle-neuronal-fat tissue axis that drives metabolic adaptation to high-sugar conditions by modulating insulin secretion and adipocyte insulin sensitivity, highlighting mechanisms that may be exploited for the development of strategies for the treatment and reversal of insulin resistance.

physiology↗

bioRxiv2022

NHA1 is a cation/proton antiporter essential for the water-conserving functions of the rectal complex in Tribolium castaneum

More than half of all extant metazoan species on earth are insects. The evolutionary success of insects is intrinsically linked with their ability to osmoregulate, suggesting that they have evolved unique physiological mechanisms to maintain water balance. In beetles (Coleoptera)--the largest group of insects--a specialized rectal ( cryptonephridial) complex has evolved that recovers water from the rectum destined for excretion and recycles it back to the body. However, the molecular mechanisms underpinning the remarkable waterconserving functions of this system are unknown. Here, we introduce a transcriptomic resource, BeetleAtlas.org, for red flour beetle Tribolium castaneum, and demonstrate its utility by identifying a cation/H+ antiporter (NHA1) that is enriched and functionally significant in the Tribolium rectal complex. NHA1 localizes exclusively to a specialized cell type, the leptophragmata, in the distal region of the Malpighian tubules associated with the rectal complex. Computational modelling and electrophysiological characterization in Xenopus oocytes show that NHA1 acts as an electroneutral K+/H+ antiporter. Furthermore, genetic silencing of Nha1 dramatically increases excretory water loss and reduces organismal survival during desiccation stress, implying that NHA1 activity is essential for maintaining systemic water balance. Finally, we show that Tiptop, a conserved transcription factor, regulates NHA1 expression in leptophragmata and controls leptophragmata maturation, illuminating the developmental mechanism that establishes the novel functions of this cell. Together, our work provides the first insights into the molecular architecture underpinning the function of one most powerful water-conserving mechanisms in nature, the beetle rectal complex. Significance StatementBeetles are the largest group of insects, inhabiting a wide range of habitats on earth. Unique adaptations in overcoming water stress is critical to their success, yet the mechanisms underpinning this ability are unknown. Using genetics, electrophysiology, imaging and behavioral studies we show that a cation/H+ (NHA1) transporter is exclusively localized to specialized cell type, the leptophragmata, in the Malpighian tubules associated with the rectal complex. Ion transport functions of NHA1 in leptophragmata underpin the movement of water from the rectum, from where it would be destined for excretion, to the Malpighian tubule and then recycled back to the body. This water recovery capability of rectal complex is essential for maintaining systemic water balance in beetles. This work provides the first insight into to the molecular architecture of one of most powerful water-conservation mechanisms in biology, and provides an important clue to the ecological and evolutionary success of the beetles.

systems biology↗

bioRxiv2022

A gut-derived hormone switches dietary preference after mating in Drosophila

Animals must adapt their dietary choices to meet their nutritional needs. How these needs are detected and translated into nutrient-specific appetites that drive food-choice behaviors is poorly defined. Here, we show that the enteroendocrine cells (EECs) of the adult female Drosophila midgut sense nutrients and in response release neuropeptide F (NPF), an ortholog of mammalian NPY-family gut-brain hormones. Gut-derived NPF acts via effects on glucagon-like adipokinetic hormone (AKH) signaling to induce sugar satiety and to drive hunger for protein-rich food, and on adipose tissue to promote storage of ingested nutrients. Suppression of gut NPF leads to overconsumption of dietary sugar while decreasing intake of protein-rich yeast. Furthermore, we show a female-specific function of gut-derived NPF in the suppression of AKH signaling after mating. This induces a dietary switch that promotes preference for protein-containing food to support reproduction. Together, our findings suggest that the gut NPF-AKH axis regulates appetite that drives specific food choices to ensure homeostatic consumption of nutrients, providing insight into the hormonal mechanisms that underlie nutrient-specific hungers.

animal behavior and cognition↗