Proteomic profile of hippocampal growth cones through early postnatal development.

Axonal growth cones rely on local proteomic changes to interpret guidance cues while navigating towards their synaptic targets. Yet the developmental dynamics of their proteome remain poorly understood. By isolating growth cones from the whole mouse hippocampus and dentate gyrus at early postnatal days, we performed a systematic characterization of their proteome. We show that growth cones from both subregions share a proteomic signature at postnatal day (P) 1, dominated by energy metabolism and protein synthesis, before taking distinct developmental trajectories. In fact, hippocampal growth cones undergo a rapid transition, from RNA-related processes to synapse formation. Dentate gyrus growth cones, however, maintain a similar proteomic profile at P3 and P5, suggesting a prolonged exploratory behaviour, consistent with later ingrowth of entorhinal cortex fibres. At these early timepoints, hippocampal and dentate gyrus growth cones are characterized by several temporally regulated proteins, suggesting dynamic and different developmental trajectories. Our dataset provides a comprehensive proteomic resource for understanding growth cone function during hippocampal circuit formation and insights into the molecular mechanisms underlying region-specific developmental timelines.