The Glial Coupling in the Developing Brain: Astrocytes, Oligodendrocytes and Myelin Formation

Astrocytes and oligodendrocytes contribute to the metabolic, homeostatic and structural organization of the developing brain, yet their interactions evolve across development and remain incompletely characterized during the earliest stages of life. This narrative review examines astrocyte–oligodendrocyte coupling in relation to myelin development and addresses the question of which cellular and metabolic mechanisms support oligodendrocyte maturation and white-matter metabolism before mature astrocytic functions are fully established. Evidence from preterm and ill term neonates is considered together with experimental and adult or elderly studies used exclusively for secondary mechanistic comparison. Astrocytes and oligodendrocytes participate in interconnected metabolic, developmental and homeostatic processes, while perinatal white-matter injury may combine reactive astrogliosis, pre-oligodendrocyte injury and maturation arrest. Neuroimaging, including quantitative susceptibility mapping, synthetic MRI, cranial ultrasound and molecular or myelin-sensitive imaging, provides complementary but indirect information on the structural and maturational consequences of these processes, whereas omics approaches may characterize their molecular environment. Radiomics similarly provides indirect tissue-level biomarkers rather than cell-specific measures of glial biology. Dysglycaemia further illustrates the dependence of developing white matter on coordinated cellular energy handling and the potential relevance of immature astrocyte–oligodendrocyte interactions during metabolic instability. Evidence from very early development suggests that oligodendrocyte maturation occurs within a changing cellular environment in which astroglial maturation, neuronal and vascular processes, and immune and metabolic mechanisms coexist. The Crossword and Foil Effects are proposed as hypothesis-generating frameworks to organize these intersecting developmental, metabolic, cellular, imaging and molecular dimensions rather than as experimentally validated causal models. Overall, no single cellular substitute for mature astrocytic functions is identified; instead, oligodendrocyte maturation appears to emerge within a developmentally changing division of metabolic, homeostatic and signaling labour across astroglial, neuronal, vascular and immune compartments.