AP2γ: a new player on adult hippocampal neurogenesis regulation

Abstract

Since the recognition that the mammalian brain retains the ability to generate newborn neurons with functional relevance throughout life, the matrix of molecular regulators that govern adult neurogenesis has been the focus of much interest. In a recent study published in Molecular Psychiatry, we demonstrate Activating Protein 2γ (AP2γ), a transcription factor previously implicated in cell fate determination in the developing cortex, as a novel player in the regulation of glutamatergic neurogenesis in the adult hippocampus. Using distinct experimental approaches, we showed that AP2γ is specifically present in a subpopulation of transient amplifying progenitors, where it acts as a crucial promoter of proliferation and differentiation of adult-born glutamatergic granule neurons. Strikingly, deficiency of AP2γ in the adult brain compromises the generation of new glutamatergic neurons, with impact on the function of cortico-limbic circuits. Here, we share our view on how AP2γ integrates the transcriptional orchestration of glutamatergic neurogenesis in the adult hippocampus, and consequently, how it emerges as a novel molecular candidate to study the translation of environmental pressures into alterations of brain neuroplasticity in homeostatic, but also in neuropathological contexts.