Neural tube closure (neurulation) is an important step in brain development and involves the progressive differentiation of neuroectodermal precursors into more specialised cell types. However, the development of other embryonic tissues concurrently with neurulation constantly alters the metabolic conditions that neuroectodermal precursors are exposed to. Now, Maria Lehtinen and co-workers describe how mitochondria adapt to their changing environment during the specification of the early mouse forebrain. Using transmission electron microscopy, they show that mitochondrial morphology in neuroepithelial cells before neurulation (at E8.5) resembles a state that favours glycolysis, whereas mitochondrial structure after neurulation (at E10.5) appears to support oxidative phosphorylation. Indeed, through transcriptional profiling of forebrain precursor cells and analysis of protein levels in the cerebrospinal fluid, they demonstrate the upregulation of glycolytic proteins at E8.5, while components of the oxidative phosphorylation machinery predominate at E10.5. Moreover, E8.5 precursors show a greater metabolic capacity for glycolysis, whereas E10.5 precursors are dependent on oxidative phosphorylation for their metabolism. The authors further demonstrate that the changes in mitochondrial morphology during neurulation rely on the downregulation of the transcription factor MYC. Collectively, these results progress our knowledge of mitochondrial metabolism during neuroectodermal precursor differentiation and contribute to our understanding of the pathological consequences that alterations in cellular metabolic environments during early forebrain development may have.
