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Lopez, D. H.

Publications and source records attributed to Lopez, D. H..

3 recordsLinked to original sources

A Fine-Tuned Phosphatidylinositol Profile Contributes to Colonocyte Differentiation and Malignization: Evidence From Integrated Omics

Membrane lipid composition changes concomitantly with human colonocyte differentiation, a tightly regulated process occurring along the colon crypt. This process is heavily disrupted in colon cancer. Nonetheless, the regulatory mechanisms driving these changes, especially the replacement of arachidonic acid phosphatidylinositol species with monounsaturated fatty acid species, and how they are altered in cancer, remain unknown. To establish the transcriptional networks underlying this remodeling, we integrated transcriptomic and lipidomic profiles of isolated healthy and tumor human colonocytes using system biology approaches; identifying key gene regulatory networks involved in arachidonic acid and eicosanoid metabolism and phosphatidylinositol cycle as significant regulators during differentiation. Consistently, a distinct impact was found on organoid differentiation depending on colonocyte subtype and specific prostaglandin. Remarkably, the shift and associated transcriptomic programs were lost in tumor that heightened phosphoinositide metabolism. Altogether, these results underscore the importance of lipid remodeling in colonocyte stemness maintenance and proper onset of differentiation programs.

systems biology↗

FETCH enables fluorescent labeling of membrane proteins in vivo with spatiotemporal control in Drosophila

Fluorescent labeling approaches are crucial for elucidating protein function and dynamics. While enhancer trapping in Drosophila has been useful for the characterization of gene transcription, protein-specific visualization in vivo has been more elusive. To overcome these limitations, we developed Fluorescent Endogenous Tagging with a Covalent Hook (FETCH) to label cell surface proteins (CSPs) in vivo through a stable covalent bond mediated by the DogTag-DogCatcher peptide partner system1. FETCH leverages a spontaneous covalent isopeptide bond that forms between the 23-amino acid DogTag and the 15-kDa DogCatcher. Unlike most tags that work best at protein termini, DogTag is optimized for function in protein loops, expanding the range of sites that can be targeted in proteins. In FETCH, DogTag is introduced into extracellular loops of CSPs through genome engineering, enabling covalent bond formation with a genetically encoded DogCatcher-GFP fusion protein that can be secreted from a variety of cell types. We describe a flow cytometry-based platform for the identification of efficient DogTag insertion sites in vitro and demonstrate the ability to visualize both tagged DIP- and Dpr10 in vivo, two immunoglobulin superfamily proteins that facilitate neuronal target recognition at Drosophila neuromuscular junctions and brain synapses. The versatility of FETCH enables fluorescent labeling with precise temporal and spatial control in vivo, enabling applications previously unfeasible.

neuroscience↗

Evolution of limb development in cephalopod mollusks

Cephalopod mollusks evolved numerous anatomical innovations, including specialized arms and tentacles, but little is known about the developmental mechanisms underlying the evolution of cephalopod limbs. Here we show that all three axes of cuttlefish limbs are patterned by the same signaling networks that act in vertebrates and arthropods, although they evolved limbs independently. In cuttlefish limb buds, Hedgehog is expressed anteriorly. Posterior transplantation of Hedgehog-expressing cells induced mirror-image limb duplications. Bmp and Wnt signaling, which establishes dorsoventral polarity in vertebrate and arthropod limbs, is similarly polarized in cuttlefish. Inhibition of the dorsal Bmp signal caused ectopic expression of Notum, a ventral sucker field marker, and development of ectopic suckers. Cuttlefish limbs also show proximodistally regionalized expression of Htx, Exd, Dll, Dac, Sp8/9, and Wnt genes, which delineate arm and tentacle sucker fields. These results suggest that cephalopod limbs evolved by parallel activation of an ancient genetic program for appendage development that was present in the bilaterian common ancestor.

developmental biology↗