Glucocorticoids and cell fate in the developing brain: Neuroendocrine mechanisms shaping developmental trajectories.

Early life stress (ELS) is a major risk factor for later psychiatric and neurological disorders. Glucocorticoids (GCs), the hormonal end-products of the neuroendocrine stress response, are central mediators of this risk, influencing how the developing brain grows and adapts. Research has shown that GCs affect processes such as cell proliferation, neuronal survival, and maturation, but much less attention has been given to whether they also shape cell fate-the developmental choices that determine whether stem and progenitor cells give rise to neurons, astrocytes, oligodendrocytes, or other specialised lineages. In this perspective, I argue that cell fate provides a valuable new lens for understanding how stress becomes embedded in brain architecture. Because GCs act directly on neural stem and progenitor populations, it is plausible that their influence extends beyond the quantity of cells produced, to the identities that emerge. I outline an initial framework for interpreting potential effects of GCs on fate, review emerging evidence from different model systems, and consider mechanisms by which stress hormones could alter developmental trajectories. By focusing on fate, this article highlights a novel dimension of neuroendocrine influence on brain development, with implications for how early experiences confer vulnerability, or resilience, to later mental health outcomes.