The altered expression of perineuronal net elements during neural differentiation

Abstract

BackgroundPerineuronal nets (PNNs), which are localized around neurons during development, are specialized forms of neural extracellular matrix with neuroprotective and plasticity-regulating roles. Hyaluronan and proteoglycan link protein 1 (HAPLN1), tenascin-R (TNR) and aggrecan (ACAN) are key elements of PNNs. In diseases characterized by neuritogenesis defects, the expression of these proteins is known to be downregulated, suggesting that PNNs may have a role in neural differentiation.MethodsIn this study, the mRNA and protein levels of HAPLN1, TNR and ACAN were determined and compared at specific time points of neural differentiation. We used PC12 cells as the in vitro model because they reflect this developmental process.ResultsOn day 7, the HAPLN1 mRNA level showed a 2.9-fold increase compared to the non-differentiated state. However, the cellular HAPLN1 protein level showed a decrease, indicating that the protein may have roles in neural differentiation, and may be secreted during the early period of differentiation. By contrast, TNR mRNA and protein levels remained unchanged, and the amount of cellular ACAN protein showed a 3.7-fold increase at day 7. These results suggest that ACAN may be secreted after day 7, possibly due to its large amount of post-translational modifications.ConclusionsOur results provide preliminary data on the expression of PNN elements during neural differentiation. Further investigations will be performed on the role of these elements in neurological disease models.

The amniotic fluid proteome changes with gestational age in normal pregnancy: a cross-sectional study

“…The most down-regulated AF proteins at term compared to midtrimester were HAPLN1, AFP, and LRP1B. HAPLN1 stabilizes the interactions between hyaluronic acid and proteoglycans, such as aggrecan and versican, in the extracellular matrix 79 – 81 , and the biological functions of HAPLN1 during fetal growth include chondrocyte differentiation and cartilage development 82 , heart development 83 , neural differentiation 84 , and neocortical folding 85 . LRP1B is a cell-surface receptor involved in receptor-mediated endocytosis 86 , expressed in the fetal brain 87 , where it may regulate apolipoprotein-mediated cholesterol uptake 88 .…”

Extracellular Matrix Remodeling in the Retina and Optic Nerve of a Novel Glaucoma Mouse Model

“…The glycoprotein tenascin-R is predominantly expressed by optic nerve oligodendrocytes and horizontal cells of the retina [28,38,39]. Tenascin-R can influence neurite outgrowth as well as neural and glial adhesion [35][36][37]. A domain-specific neuroprotective effect of tenascin-R has been described, presumably by regulation of microglia behavior [71].…”

“…Tenascin-R can influence neurite outgrowth as well as neural and glial adhesion [35][36][37]. In the retina, tenascin-R is released by horizontal cells and accumulates in the plexiform layers.…”

Hapln1b, a central organizer of the ECM, modulates kit signaling to control developmental hematopoiesis in zebrafish

“…37 Knockout mouse studies have also revealed a role in maintaining perineural nets (PNNs), a hyaluronan backbone meshlike network of proteins that surround neurons and regulate neuronal plasticity, 38 as well as neural differentiation and development. [39][40][41] Furthermore, PNNs are responsible for binding chemorepulsive molecules, such as Semaphorin3a, 42 and transcription factors, such as Otx2, that are exchanged between different neural cells to enhance cortical plasticity. 43 Hapln1a was recently shown to be necessary for ECM expansion in the developing zebrafish heart, and CRISPR-Cas9 hapln1a mutants show reduced atrial size and chamber ballooning.…”