GRASPs link Reelin to the Golgi during neocortical development to control neuronal migration and dendritogenesis.

Abstract

Reelin serves as a crucial regulator of brain organogenesis, playing a significant role in neuronal positioning and dendritogenesis. At subcellular level, it influences the translocation and remodeling of the Golgi apparatus. Despite its importance, the mechanisms by which Reelin governs the Golgi during neuronal migration and dendrite formation remain largely unknown. This study reveals that Reelin promotes de novo translation of Golgi Re-Assembly Stacking Proteins (GRASPs), which are essential for the functions of Reelin on cortical neurons. Downregulation of GRASPs in migrating excitatory neurons of the embryonic neocortex leads to disoriented cells during the multipolar phase of migration and an aberrant leading process length during locomotion. Postnatally, it results in mislocalized neurons displaying a disorganized Golgi structure and an improperly oriented, underdeveloped apical dendrite. Our findings position GRASPs and their role in Golgi morphology modulation as novel contributors to the Reelin-mediated processes during embryonic development of the mammalian neocortex.