Research Projects

Embryonic development and patterning is the output of genes getting expressed in a strict spatiotemporal manner. Cellular fate in a morphogenetic field is specified by morphogen gradients. In the context of such a gene centric view of development, the role of cellular metabolism is now coming to the fore. Our previous study showed the presence of a glycolytic gradient along the anterior-posterior axis of mouse embryonic presomitic mesoderm (PSM) that drives axial elongation (Bulusu et al., 2017). Such a metabolic gradient might help in nutrient sensing and shape developmental programs accordingly. Our hypothesis is that such metabolic gradients are more ubiquitous in embryos. This proposal is aimed at identifying glycolytic gradients in other morphogenetic fields and understanding their interplay with morphogen gradients. Preliminary data from in situ hybridization shows that aldolase A (enzyme that catalyzes the committed step of glycolysis) is expressed in a graded manner from distal end to proximal end of the limb bud in chick embryo. The gradient will be tested at the activity level by imaging and mass spectrometry based approaches. The mechanism of formation of glycolytic gradient will be studied by genetic and pharmacological manipulation of Wnt and FGF signaling that are also high in the distal end than the proximal end. Finally the role of glycolysis in proliferation and differentiation of limb mesenchyme cells will be studied using in ovo and limb explant culture models. Results from this study will strengthen the understanding of gene-environment interaction in shaping development. Maternal nutrition impacts development but the mechanistic details at the cellular level are largely unknown. Understanding this regulation will help in better approaches to tackle embryopathies originating due to maternal diabetes and malnutrition