Glycogen supports glycolytic plasticity in morphogenetic blastemal cells

It has long been assumed that glycogen in developing organisms is primarily stored within supportive lineages such as the yolk syncytial layer, with limited direct relevance to the cells that drive tissue morphogenesis. Yet, recent work has implicated glycogen in patterning cell physiology. Here, we extend these findings, demonstrating that morphogenetically active cells directly catabolize glycogen to sustain glycolysis in vivo. Using a genetically encoded metabolic biosensor in Caenorhabditis elegans embryos, we uncover a cell-intrinsic, glycogen-dependent glycolytic plasticity that is selectively engaged during hypoxia and mitochondrial compromise. This direct cellular use of glycogen is essential for maintaining intercellular patterning cues, revealing an unexpected and critical role for glycogen in developmental energy metabolism. Glycogen represents the largest energy reserve in the embryo, but its specific contribution to the energetic economy of morphogenetic cells in vivo remains poorly understood. We established a platform in Caenorhabditis elegans to dynamically interrogate glycolytic states within single blastomeres of living embryos via the glycolytic sensor HYlight and determined that morphogenetic cells can rapidly modulate glycolysis in response to mechanical activity or transient hypoxia. Through an RNAi screen we found that PYGL-1, the worm orthologue of human glycogen phosphorylase, is required in these cells for glycolytic plasticity. We determined that cells employ at least two modes of glycolytic plasticity: glycogen-dependent glycolytic plasticity (GDGP) and glycogen-independent glycolytic plasticity. GDGP is selectively deployed under conditions of mitochondrial dysfunction, such as transient hypoxia or in strains carrying lesions in the respiratory chain. Loss of GDGP abrogates glycolytic plasticity and is associated with defects in secretory vesicle recycling and distribution of morphogens during hypoxia. Together, our study demonstrates that morphogenetic cells in vivo can directly utilize glycogen as a fuel to sustain glycolytic plasticity and the signaling dynamics that drive tissue patterning.