Systematic expression analysis of plasticity‐related genes in mouse brain development brings PRG4 into play

Abstract

Background Plasticity‐related genes (Prgs/PRGs) or lipid phosphate phosphatase‐related proteins (LPPRs) comprise five known members, which have been linked to neuronal differentiation processes, such as neurite outgrowth, axonal branching, or dendritic spine formation. PRGs are highly brain‐specific and belong to the lipid phosphate phosphatases (LPPs) superfamily, which influence lipid metabolism by dephosphorylation of bioactive lipids. PRGs, however, do not possess enzymatic activity, but modify lipid metabolism in a way that is still under investigation. Results We analyzed mRNA expression levels of all Prgs during mouse brain development, in the hippocampus, neocortex, olfactory bulbs, and cerebellum. We found different spatio‐temporal expression patterns for each of the Prgs, and identified a high expression of the uncharacterized Prg4 throughout brain development. Unlike its close family members PRG3 and PRG5, PRG4 did not induce filopodial outgrowth in non‐neuronal cell lines, and does not localize to the plasma membrane of filopodia. Conclusion We showed PRG4 to be highly expressed in the developing and the adult brain, suggesting that it is of vital importance for normal brain function. Despite its similarities to other family members, it seems not to be involved in changes of cell morphology; instead, it is more likely to be associated with intracellular signaling.

Plasticity-Related Gene 5 Is Expressed in a Late Phase of Neurodifferentiation After Neuronal Cell-Fate Determination

“…These processes occur in the adult brain in regions in which we found high PRG5 abundance, supporting a similar function for the endogenous PRG5 protein in the brain. Consistent with previous mRNA-expression analysis in primary cultured brain cells, we found PRG5 protein to be primarily expressed in neurons and in an oligodendrocyte subtype, but not in astrocytes (Coiro et al, 2014;Gross et al, 2021). In neurons, we found PRG5 in both excitatory and inhibitory cells.…”

“…We previously analyzed PRG1-5 expression on the mRNA level during mouse brain development via quantitative RT-PCR and found expression patterns to be dynamic (Velmans et al, 2013;Coiro et al, 2014;Gross et al, 2021). Here, we confirm a developmental regulation also for the PRG5 protein in cortex lysates from developmental stages E14 to P60 (Figure 2A).…”

“…in the brain (Figure 4C, white arrow heads). On the other hand, we had previously demonstrated PRG5 mRNA expression in primary immature and mature cultured oligodendrocytes (Gross et al, 2021). In immunostaining of brain sections, we found PRG5 protein in a subtype of oligodendrocytes in the corpus callosum (cc), but we could not detect a PRG5 signal in axonal fibers of the cc, marked by NF-M (Figure 4D, white arrow heads).…”

“…Using qRT-PCR, PRGs have been shown to be developmentally regulated on the mRNA level (Bräuer et al, 2003;Velmans et al, 2013;Coiro et al, 2014;Gross et al, 2021). We analyzed PRG5-protein expression during cortex development and found a developmental regulation, with increasing expression from late embryonic stages onward.…”

“…PRG5 (synonyms: LPPR5, PAP2D) mRNA is strongly expressed during mouse brain development, where it peaks around birth and slightly decreases toward adult stages. Only in areas of high synaptic plasticity and adult neurogenesis does PRG5 expression remain elevated (Coiro et al, 2014;Gross et al, 2021). In vitro analysis of developing hippocampal neurons showed a shift in expression, from an equal distribution along all neurites toward increased localization only along dendrites (Broggini et al, 2010;Coiro et al, 2014).…”