Biology subjects

Avellaneda, J.

Publications and source records attributed to Avellaneda, J..

4 recordsLinked to original sources

bioRxiv2025

Cell type specific allometry controls sex-differences in Drosophila body size

Species and sex-specific differences in organ size are fundamental features of animal biology, yet the mechanisms that drive these differences remain debated. Adult female Drosophila are larger than males. While most organs are present across both sexes, the underlying mechanisms driving sex-specific organ and body size scaling of Drosophila remain unclear. Using single-nucleus transcriptomes from the Fly Cell Atlas, combined with experimental validation, we show that different Drosophila organs scale through distinct strategies, including cell size, cell number, or a combination of both, in an allometric rather than uniform manner. Larger female flight muscles develop from more myoblasts than in males, while cardiomyocyte numbers are the same despite forming a larger heart in females. Female fat body cells are larger and express more ribosomal protein-coding mRNAs, supporting increased cell size. In contrast, males have a greater number of fat body cells. Together, this sex-specific allometry in cell size and number define the cellular basis for differences in body and organ size between sexes in Drosophila. By uncovering how a conserved developmental system produces sex-specific proportions through distinct cellular strategies, our work offers a framework for dissecting sex differences in other species and systems.

cell biology↗

bioRxiv2024

Microtubules coordinate mitochondria transport with myofibril morphogenesis during muscle development

Muscle morphogenesis creates highly specialised muscle cells containing contractile myofibrils and energy producing mitochondria. Myofibrils are chains of sarcomeres, whose myosin motors slide over actin filaments at the expense of ATP. Thus, myofibrils and mitochondria are in intimate contact in mature muscles. However, how mitochondria morphogenesis is coordinated with myofibrillogenesis during development remains largely unknown. Here, we used in vivo imaging to investigate myofibril and mitochondria network dynamics in developing Drosophila flight muscles. We found that mitochondria rapidly intercalate from the surface of actin bundles to their interior; concomitantly, actin filaments condense to individual myofibrils. This ensures that mitochondria are in intimate proximity to each myofibril. Interestingly, antiparallel microtubules bundle in concert with the assembling myofibrils, suggesting a key role in myofibril orientation. Indeed, light-induced microtubule severing directly affects myofibril orientation, whereas knock-down of kinesin heavy chain specifically blocks mitochondria intercalation and long-range transport. Importantly, mitochondria-myofibril intercalation and microtubule-based transport of mitochondria is conserved in developing mammalian muscle. Together, these data identify a key role for microtubules in coordinating mitochondria and myofibril morphogenesis to build functional muscles.

developmental biology↗

bioRxiv2023

A mechanically regulated liquid-liquid phase separation of the transcriptional regulator Tono instructs muscle development

Muscle morphogenesis is a multi-step program, starting with myoblast fusion, followed by myotube-tendon attachment and sarcomere assembly, with subsequent sarcomere maturation, mitochondrial amplification and specialisation. The correct chronological order of these steps requires precise control of the transcriptional regulators and their effectors. How this regulation is achieved during muscle development is not well understood. In a genome-wide RNAi screen in Drosophila, we identified the BTB-zinc finger protein Tono (CG32121) as a muscle-specific transcriptional regulator. tono mutant flight muscles display severe deficits in mitochondria and sarcomere maturation, resulting in uncontrolled contractile forces causing muscle atrophy during development. Tono protein is expressed during sarcomere maturation and localises in distinct condensates in flight muscle nuclei. Interestingly, internal pressure exerted by the maturing sarcomeres deforms the muscle nuclei into elongated shapes and changes the Tono condensates, suggesting that Tono senses the mechanical status of the muscle cells. Indeed, external mechanical pressure on the muscles triggers rapid liquid-liquid phase separation of Tono utilising its BTB domain. Thus, we propose that Tono senses high mechanical pressure to in turn adapt muscle transcription specifically at the sarcomere maturation stage. Consistently, tono mutant muscles display specific defects in a transcriptional switch that represses early muscle differentiation genes and boosts late ones. We hypothesise that a similar mechano-responsive regulation mechanism may control the activity of related BTB-zinc finger proteins that, if mutated, can result in uncontrolled force production in human muscle.

developmental biology↗

bioRxiv2020

Myofibril and mitochondria morphogenesis are coordinated by a mechanical feedback mechanism in muscle

Complex animals build specialised muscle to match specific biomechanical and energetic needs. Hence, composition and architecture of sarcomeres as well as mitochondria are muscle type specific. However, mechanisms coordinating mitochondria with sarcomere morphogenesis are elusive. Here we use Drosophila muscles to demonstrate that myofibril and mitochondria morphogenesis are intimately linked. In flight muscles, the muscle selector spalt instructs mitochondria to intercalate between myofibrils, which in turn mechanically constrain mitochondria into elongated shapes. Conversely in cross-striated muscles, mitochondria networks surround myofibril bundles, contacting myofibrils only with thin extensions. To investigate the mechanism causing these differences, we manipulated mitochondrial dynamics and found that increased mitochondrial fusion during myofibril assembly prevents mitochondrial intercalation in flight muscles. Strikingly, this coincides with the expression of cross-striated muscle specific sarcomeric proteins. Consequently, flight muscle myofibrils convert towards a partially cross-striated architecture. Together, these data suggest a biomechanical feedback mechanism downstream of spalt synchronizing mitochondria with myofibril morphogenesis.

developmental biology↗