Biology subjects

Marvaldi, L.

Publications and source records attributed to Marvaldi, L..

4 recordsLinked to original sources

bioRxiv2025

Paw posture is a robust indicator for injury, pain, and age.

Inferring biological states from animal behavior is a crucial but challenging step in biomedical discovery that is constrained by variability and labour-intensive assays, even with AI-powered tools. Here, we show that simple images of static paws, analyzed by our custom keypoint segmentation AI-tool provide accurate read-outs for a wide array of physiological states. Without invasive testing, our method detects postural changes associated with nerve injury, acute pain, aging, and the genetic loss of kpna4, a regulator of paw innervation. Leveraging the toe-spread-reflex, a spinal-circuit driven response, the approach requires no habituation and shows low behavioral variability. Individual digits emerge as biomarkers for internal states with digit V indicating neuropathic pain during nerve damage and digit I reflecting loss of kpna4. Our model is freely available and can readily be adapted to other tasks or species. These findings establish unstimulated paw posture as a scaleable, low-cost, readout for biological states.

neuroscience↗

bioRxiv2022

A conditional null allele of Dync1h1 enables targeted analyses of dynein roles in neuronal length sensing and neurological disorders

Size homeostasis is one of the most fundamental aspects of biology and it is particularly important for large cells as neurons. We have previously proposed a motor-dependent length-sensing and growth-regulating mechanism wherein a partial reduction in the levels of microtubule motor proteins should lead to accelerated neuronal growth. This prediction was originally validated in sensory neurons heterozygous for the Loa point mutation in dynein heavy chain 1 (Dync1h1Loa). Here we describe a new mouse model with a conditional allele allowing deletion of exons 24-25 in Dync1h1. Homozygous Islet1-Cre deletion of Dync1h1 is embryonic lethal, but heterozygous animals (Isl1-Dync1h1+/-) survive to adulthood with approximately 50% dynein expression in targeted cell types. Isl1-Dync1h1+/- adult sensory neurons reveal an accelerated growth phenotype, similar to that previously reported in Dync1h1Loa neurons. Moreover, Isl1-Dync1h1+/- mice show mild impairments in gait, proprioception and tactile sensation; and slightly impaired recovery from peripheral nerve injury. Thus, conditional deletion of Dync1h1 exons 24-25 enables targeted studies of the role of dynein in neuronal growth and neurological disorders.

neuroscience↗

bioRxiv2020

PTBP1 Regulates Injury Responses and Sensory Pathways in Adult Peripheral Neurons

Polypyrimidine Tract Binding Protein 1 (PTBP1) is expressed only at embryonic stages in central neurons. Its downregulation triggers neuronal differentiation in precursor and non-neuronal cells, an approach recently used to generate neurons de novo for amelioration of neurodegenerative disorders. Moreover, PTBP1 is replaced by its paralog PTBP2 in mature central neurons. Surprisingly, we found both proteins co-expressed in adult sensory and motor neurons, with PTBP2 restricted mainly to the nucleus, while PTBP1 shows strong axonal localization. Levels of axonal PTBP1 increased markedly after peripheral nerve injury, and its cargos include mRNAs involved in axonal growth and regeneration, such as importin {beta}1 and RhoA. Perturbation of PTBP1 affects neuronal injury responses, axon outgrowth and sensation in vivo. Thus, PTBP1 has roles in sensory function and regenerative capacity of adult sensory neurons. These findings suggest that caution may be required before considering targeting PTBP1 for therapeutic purposes.

neuroscience↗

bioRxiv2019

DYNLRB1 is Essential for Dynein Mediated Transport and Neuronal Survival

The cytoplasmic dynein motor complex transports essential signals and organelles from the cell periphery to perinuclear region, hence is critical for the survival and function of highly polarized cells such as neurons. Dynein Light Chain Roadblock-Type 1 (DYNLRB1) is thought to be an accessory subunit required for specific cargos, but here we show that it is essential for general dynein-mediated transport and sensory neuron survival. Homozygous Dynlrb1 null mice are not viable and die during early embryonic development. Furthermore, heterozygous or adult knockdown animals display reduced neuronal growth, and selective depletion of Dynlrb1 in proprioceptive neurons compromises their survival. Conditional depletion of Dynlrb1 in sensory neurons causes deficits in several signaling pathways, including {beta}-catenin subcellular localization, and a severe impairment in the axonal transport of both lysosomes and retrograde signaling endosomes. Hence, DYNLRB1 is an essential component of the dynein complex.

neuroscience↗