Developmental Time, Cultural Space by Howard F. Stein

Combined, we propose that FBP functions as a flux-signaling metabolite connecting glycolysis and PSM patterning, potentially through modulating subcellular protein localization. Specifically, we revealed that FBP supplementation caused depletion of Pfkl and Aldoa from the nuclear-soluble fraction. To probe for mechanisms underlying glycolytic flux-signaling, we performed subcellular proteome analysis and revealed that cytoPFKFB3 overexpression altered subcellular localization of certain proteins, including glycolytic enzymes, in PSM cells. Overexpression of cytoPFKFB3 indeed led to increased glycolytic flux/FBP levels and caused an impairment of mesoderm segmentation, paralleled by the downregulation of Wnt-signaling, reminiscent of the effects seen upon FBP-supplementation.

To genetically manipulate glycolytic flux and FBP levels, we generated a mouse model enabling the conditional overexpression of dominant active, cytoplasmic PFKFB3 (cytoPFKFB3). We found that medium-supplementation with FBP, but not with other glycolytic metabolites, such as fructose 6-phosphate and 3-phosphoglycerate, impaired mesoderm segmentation. First, we identified fructose 1,6-bisphosphate (FBP) as an in vivo sentinel metabolite that mirrors glycolytic flux within PSM cells of post-implantation mouse embryos. Here, we investigated how glycolytic flux impacts embryonic development, using presomitic mesoderm (PSM) patterning as the experimental model. Urn:isbn:0915042061 Republisher_date 20160720174642 Republisher_operator Republisher_time 1379 Scandate 20160702101044 Scanner cellular metabolic state impacts cellular programs is a fundamental, unresolved question. OL2746930W Page-progression lr Page_number_confidence 88.26 Pages 266 Ppi 300 Related-external-id urn:isbn:0915042053 Access-restricted-item true Addeddate 18:50:00.219508 Bookplateleaf 0004 Boxid IA1147919 City Norman Donorīostonpubliclibrary Edition 1st ed.

Developmental Time, Cultural Space by Howard F. Stein