Reassessing forebrain organization: recent evidence challenges the prosomere model

For over three decades, the prosomere model has influenced our understanding of vertebrate brain development by proposing that the forebrain consists of several transverse segments, termed prosomeres. However, advances in molecular genetics and imaging have challenged key assumptions of this model, including the existence of clear segmental boundaries and the positioning of forebrain axes. Here we critically review evidence from gene expression, fate-mapping, and morphogenesis studies, finding limited support for prosomeric segmentation and questioning the grouping of the hypothalamus with the telencephalon. We propose the tripartite hypothalamus model as an alternative framework that better aligns with recent data, restoring the hypothalamus's relationship to the diencephalon and recognizing the anterior forebrain as a uniquely complex, non-segmented unit with a posterior boundary within the diencephalon. These findings suggest a need to revise our understanding of forebrain structure, patterning, and evolution.