Biology subjects

Beaven, R.

Publications and source records attributed to Beaven, R..

6 recordsLinked to original sources

bioRxiv2025

Microtubule curling as an efficient readout to uncover fundamental concepts of axonal cell biology

Nerve fibres (aka axons) are the slender, up-to-meter-long processes of nerve cells that wire nervous systems. These delicate structures must survive for an organisms lifetime, making them prime lesion sites in neurodegeneration. Their long-term maintenance requires the homeostasis of complex local cell biology upheld by motor protein-driven transport along microtubule bundles that run uninterrupted along axons. To gain an understanding of axonal homeostasis, we report and discuss here the functional loss of 105 genes from a wide range of cell biological processes using a standardised Drosophila primary neuron system. [~]40% of these gene deficiencies caused microtubule bundle disturbances referred to as microtubule-curling, which we use as an indicator of axonal atrophy. Our live imaging showed that microtubule-curling initiates in areas where axons widen, such as areas close to the soma, branch points or growth cones. In wild-type neurons, any initiated curling was contained, but it persisted as growing footprints in mutant curl-promoting conditions. Closer analyses of 20 curl-promoting conditions suggested a general classification into two groups: mutations affecting axonal physiology cause ROS-mediated microtubule-curling, whereas mutations causing motor hyperactivation or affecting microtubule-regulating proteins cause structurally induced ROS-independent curling. As will be discussed, our data provide consistent support for the previously proposed dependency cycle of local axon homeostasis model which can explain the long-standing conundrum that genes from a wide range of cell biological processes often have mutational links to the same class of inherited neurodegenerative disease.

cell biology↗

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↗

bioRxiv2024

Evidence for the independent evolution of a rectal complex within the beetle superfamily Scarabaeoidea

Rectal or cryptonephridial complexes have evolved repeatedly in arthropods, including in beetles where they occur in [~]190,000 species of Cucujiformia and Bostrichoidea, and Lepidoptera where they occur in [~]160,000 species. Sections of the Malpighian/renal tubules coat the outer surface of the rectum, acting as powerful recycling systems of the gut contents, recovering water and specific solutes. There are hints that a rectal complex evolved independently within another beetle group, Scarabaeoidea. Here we report our observations of rectal complexes in Scarabaeoidea, which support this view. We did not find a rectal complex in the related group, Staphylinoidea, or in Lucanidae, a basal group of Scarabaeoidea. We did observe rectal complexes in Melolontha melolontha (Melolonthini), Pachnoda marginata and Cetonia aurata (Cetoniinae), consistent with previous reports from these groups. Intriguingly we found that rectal complexes occur in adult, but not M. melolontha larvae, and larvae but not adults within Cetoniinae, indicating dramatic pupal remodelling of these organ systems. Insights into the structure of the rectal complexes of Scarabaeoidea are compared with the well-studied rectal complexes of Cucujiformia. Finally we discuss possible functions of the rectal complexes of beetles within Scarabaeoidea, and future approaches to address this question.

evolutionary biology↗

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

Piezo buffers mechanical stress via modulation of intracellular Ca2+ handling in the Drosophila heart

Throughout its lifetime the heart is buffeted continuously by dynamic mechanical forces resulting from contraction of the heart muscle itself and fluctuations in haemodynamic load and pressure. These forces are in flux on a beat-by-beat basis, resulting from changes in posture, physical activity or emotional state, and over longer timescales due to altered physiology (e.g. pregnancy) or as a consequence of ageing or disease (e.g. hypertension). It has been known for over a century of the hearts ability to sense differences in haemodynamic load and adjust contractile force accordingly1-4. These adaptive behaviours are important for cardiovascular homeostasis, but the mechanism(s) underpinning them are incompletely understood. Here we present evidence that the mechanically-activated ion channel, Piezo, is an important component of the Drosophila hearts ability to adapt to mechanical force. We find Piezo is a sarcoplasmic reticulum (SR)-resident channel and is part of a mechanism that regulates Ca2+ handling in cardiomyocytes in response to mechanical stress. Our data support a simple model in which Drosophila Piezo transduces mechanical force such as stretch into a Ca2+ signal, originating from the SR, that modulates cardiomyocyte contraction. We show that Piezo mutant hearts fail to buffer mechanical stress, have altered Ca2+ handling, become prone to arrhythmias and undergo pathological remodelling.

physiology↗

bioRxiv2022

Early patterning followed by tissue growth establishes proximo-distal identity in Drosophila Malpighian tubules

Specification and elaboration of proximo-distal (P-D) axes for structures or tissues within a body occurs secondarily from that of the main axes of the body. Our understanding of the mechanism(s) that pattern P-D axes is limited to a few examples such as vertebrate and invertebrate limbs. Drosophila Malpighian/renal tubules (MipTs) are simple epithelial tubules, with a defined P-D axis. How this axis is patterned is not known, and provides an ideal context to understand patterning mechanisms of a secondary axis. Furthermore, epithelial tubules are widespread, and their patterning is not well understood. Here, we describe the mechanism that establishes distal tubule and show this is a radically different mechanism to that patterning the proximal MpT. The distal domain is patterned in two steps: distal identity is specified in a small group of cells at the earliest stage of MpT development through Wingless/Wnt signalling. Subsequently, this population is expanded by proliferation to generate the distal MpT domain. This mechanism enables distal identity to be established in the tubule in a domain of cells much wider than the effective range of Wingless. Summary statementHow does proximo-distal patterning occur in the epithelial Malpighian/renal tubules? Cells are patterned early by a mechanism involving Wingless/Wnt, and expand by cell proliferation to generate a distal domain.

developmental biology↗