Biology subjects

Skromne, I.

Publications and source records attributed to Skromne, I..

3 recordsLinked to original sources

bioRxiv2020

Carbon dots deposition in adult bones reveal areas of growth, injury and regeneration

C-dots synthesized from carbon nanopowder (oxidation, hydrothermal) are particularly attractive theragnostic agents for bone-related injuries and disease due to their bright fluorescence and high binding affinity and specificity for bones, as demonstrated in a larval animal model. Larval bone development, however, is significantly different from the bone growth, repair and regeneration processes occurring in adults. Using adult zebrafish, we investigated C-dots interactions with adult skeletal structures. Upon injection, C-dots were observed at the surface of bones, at sites of appositional growth. In regenerating bones, C-dots were observed at the core and on the surface of the bones depending on the age of the tissue. C-dots deposition occurred within 30 min of delivery and it was highly selective. Importantly, their deposition did not interfere with bone regeneration or the animals health. Together, these properties establish C-dots as novel tools for the diagnostic and treatment of adult bone-related injuries and diseases.

pharmacology and toxicology↗

bioRxiv2019

A theoretical model of neural maturation during the spinal cord neurogenesis

Cellular differentiation is a tightly regulated process under the control of intricate signaling and transcription factors interaction network working in coordination. These interactions make the systems dynamic, robust and stable but also difficult to dissect. In the spinal cord, recent work has shown that a network of FGF, WNT and Retinoic Acid (RA) signaling factors regulate neural maturation by directing the activity of a transcription factor network that contains CDX at its core. Here we have used partial and ordinary (Hill) differential equation based models to understand the spatiotemporal dynamics of the FGF/WNT/RA and the CDX/transcription factor networks, alone and in combination. We show that in both networks, the strength of interaction among network partners impacts the dynamics, behavior and output of the system. In the signaling network, interaction strength determine the position and size of discrete regions of cell differentiation and small changes in the strength of the interactions among networking partners can result in a signal overriding, balancing or oscillating with another signal. We also show that the spatiotemporal information generated by the signaling network can be conveyed to the CDX/transcription network to produces a transition zone that separates regions of high cell potency from regions of cell differentiation, in agreement with most in vivo observations. Importantly, both networks have built in robustness to extrinsic disturbances. This analysis provides a model for the interaction conditions underlying spinal cord cell maturation during embryonic axial elongation.

systems biology↗

bioRxiv2017

Cdx4 regulates the onset of spinal cord neurogenesis

The progressive maturation of cells down differentiation lineages is controlled by collaborative interactions between networks of extracellular signals and intracellular transcription factors. In the vertebrate spinal cord, FGF, Wnt and Retinoic Acid signaling pathways regulate the progressive caudal-to-rostral maturation of neural progenitors by regulating a poorly understood gene regulatory network of transcription factors. We have mapped out this gene regulatory network in the chicken pre-neural tube, identifying CDX4 as a dual-function core component that simultaneously regulates gradual loss of cell potency and acquisition of differentiation states: in a caudal-to-rostral direction, CDX4 represses the early neural differentiation marker Nkx1.2 and promotes the late neural differentiation marker Pax6. Significantly, CDX4 prevents premature PAX6-dependent neural differentiation by blocking Ngn2 activation. This regulation of CDX4 over Pax6 is restricted to the rostral pre-neural tube by Retinoic Acid signaling. Together, our results show that in the spinal cord, CDX4 is part of the gene regulatory network controlling the sequential and progressive transition of states from high to low potency during neural progenitor maturation. Given CDX well-known involvement in Hox gene regulation, we propose that CDX factors coordinate the maturation and axial specification of neural progenitor cells during spinal cord development.

developmental biology↗