GPR37: A Potential Regulator of Granule Cell Maturation in Hippocampal Neurogenesis

Neurogenesis is the generation and integration of new neurons into existing neural networks, happening even in adulthood. Two classical neurogenic niches are located in the subgranular zone (SGZ) and the subventricular zone (SVZ). Neurogenesis is controlled by multiple processes, including the canonical Wnt/β‐catenin signaling pathway, known for its stage-specific regulation of neurogenesis. G-Protein Coupled Receptor 37 (GPR37), an orphan GPCR known for its role as a negative regulator of oligodendrocyte differentiation and myelination, has also been reported to play a direct role GPR37 in Wnt/β‐catenin signaling by acting as a coreceptor with LRP6 .Using in-situ hybridization we verified the co-expression of LRP6 and GPR37, and with immunohistochemistry it was shown that GPR37 Knock-out (KO) mice portrayed different morphological characteristics of mature neurons in area and eccentricity than their WT counterparts. The diverse nature of the hippocampus also raises the question of the impact of GPR37-deficiency in the ventral hippocampus, which is responsible for affective behavior. Behavioral tests on the elevated plus maze results in a trend of female GPR37-KO mice exhibiting less anxiety-like behavior, and a significant increase in male GPR37-KO exhibiting more risk-assessment behavior was observed. In another anxiety-testing behavioral paradigm, the LD-Box, GPR37-KO mice spent less time in the light-compartment, indicative of an anxiogenic phenotype. The results of these cellular and behavioral components pose the question of GPPR37’s significance in behavioral phenotypes that may be a result of altered canonical Wnt-signaling in the subgranular zone.