Biology subjects

Vidal, J.

Publications and source records attributed to Vidal, J..

2 recordsLinked to original sources

bioRxiv2022

A novel mechanism for left-right asymmetry establishment involving tissue remodeling and MyoID

Left-right asymmetries have repeatedly evolved in diverse animals and affect the position, shape or size of specific organs. How novel left-right asymmetries arise remains unknown. Here, we examined Drosophila pachea, where males have evolved unique asymmetric genitalia lobes and a right-sided copulation posture in the past 3-6 million years. We found that male asymmetric lobes grow in pupae during a 360{degrees} clockwise genitalia rotation, a conserved and widespread developmental process in flies. Using two complementary approaches, drug application and a CRISPR-induced MyoID mutant, we altered genitalia rotation and found that asymmetric lobe sizes depend on genitalia rotation completion, while the sidedness of lobe asymmetry is determined by the rotation direction. We then investigated the impact of genital asymmetry on copulation posture. Males with reversed genital asymmetry still mate in the typical right-sided posture, indicating that right-sided behavior is not determined by asymmetric male genitalia. Our study reveals that a novel genitalia asymmetry has evolved through the co-option of a pre-existing tissue remodeling process. Tissue rotation represents a new mechanism, through which a bilateral organ can acquire a left-right size asymmetry. Summary statementHow asymmetric shapes evolve from symmetry is an important question in developmental biology. Using a juvenile hormone derivative, transgenics and CRISPR mutants in the non model species Drosophila pachea, we uncover that the developmental process of male genitalia rotation got co-opted during evolution of D. pachea to determine the extent and direction of a novel genital left-right asymmetry.

evolutionary biology↗

bioRxiv2021

Direct reprogramming of human fibroblasts into insulin-producing cells by transcription factors

Direct lineage reprogramming of one somatic cell into another bypassing an intermediate pluripotent state has emerged as an alternative to embryonic or induced pluripotent stem cell differentiation to generate clinically relevant cell types. One cell type of clinical interest is the pancreatic {beta} cell that secretes insulin and whose loss and/or dysfunction leads to diabetes. Generation of functional {beta}-like cells from developmentally related somatic cell types (pancreas, liver, gut) has been achieved via enforced expression of defined sets of transcription factors. However, clinical applicability of these findings is challenging because the starting cell types are not easily obtainable. Skin fibroblasts are accessible and easily manipulated cells that could be a better option, but available studies indicate that their competence to give rise to {beta} cells through similar direct reprogramming approaches is limited. Here, using human skin fibroblasts and a protocol that ensures high and consistent expression of adenovirus-encoded reprogramming factors, we show that the transcription factor cocktail consisting of Pdx1, Ngn3, MafA, Pax4 and Nkx2-2 activates key {beta} cell genes and down-regulates the fibroblast transcriptional program. The converted cells produce insulin and exhibit intracellular calcium responses to glucose and/or membrane depolarization. Furthermore, they secrete insulin in response to glucose in vitro and after transplantation in vivo. These findings demonstrate that transcription factor-mediated direct reprogramming of human fibroblasts is a feasible strategy to generate insulin-producing cells.

developmental biology↗