A dynamic gene regulatory code drives synaptic development of hippocampal granule cells [RNA-Seq]

Connecting neurons into functional circuits requires the formation, maturation, and plasticity of synapses. While advances have been made in identifying individual genes regulating synapse development, the molecular programs orchestrating their action during circuit integration of neurons remain poorly understood. Here we have employed a bulk RNA sequencing method (RiboTag) to study the development of hippocampal GCs. GCs represent the first relay in the hippocampal tri-synaptic loop, and play an essential role in processing spatial representations and memory acquisition. This study provides a high temporal resolution analysis of the translatome of GCs during early postnatal development (P5, P7, P10, P15, P21, and P28). Together, these findings highlight the networks of key TFs and target genes orchestrating GC synapse development. Hippocampi from Rbp4-Cre:RiboTag mice were homogenized and the homogenate was incubated with anti-HA magnetic beads for RPL22-HA pull down. Ribosome-bound mRNA was separated from ribosomes, RNA was isolated and libraries prepared for bulk RNA sequencing. This process was repeated at post-natal day (P)5, P7, P10, P15, P21 and P28.