Analysis of the expression and function of BRINP family genes during neuronal differentiation in mouse embryonic stem cell‐derived neural stem cells

Abstract

We previously identified a novel family of genes, BRINP1, 2, and 3, that are predominantly and widely expressed in both the central nervous system (CNS) and peripheral nervous system (PNS). In the present study, we analyzed the expression pattern of three BRINP genes during differentiation of mouse embryonic stem (ES) cell-derived neural stem cells (NSCs) and their effects on the cell-cycle regulation of NSCs. While there was no significant expression of any BRINP-mRNA expressed in mouse ES cells, BRINP 1 and 2-mRNAs was expressed at high levels in the ES cell-derived neural stem cells. Upon differentiation into neuronal cells in the presence of retinoic acid and BDNF, all three types of BRINP-mRNA were induced with a similar time course peaking at day three of treatment. Upon differentiation into astroglial cells in the presence of serum, BRINP1-mRNA was slightly up-regulated, while BRINP2- and BRINP3-mRNAs were almost abolished in the astrocytes. While 69.2, 26.1, and 7.7% of cells in a population of NSCs in the exponentially growing phase were in the G1, S and G2 phases, respectively, over-expression of any one of the three BRINP genes completely abolished cells in the G2 phase and significantly reduced the cells in S phase to 11.8-13.8%. Based on these results, the physiological roles of induced BRINP genes in the cell-cycle suppression of terminally differentiated post-mitotic neurons are discussed.

Genome-Wide Profiles of Extra-cranial Malignant Rhabdoid Tumors Reveal Heterogeneity and Dysregulated Developmental Pathways

“…Of these, 11 were differentially expressed between MRT subgroups 1 and 2 (FDR < 0.05). 10 of the 11 genes were over-expressed in subgroup 1 (Table S4), including genes linked to neuronal differentiation (e.g., BEX1 , FAM5C/BRINP3; Coyle et al, 2011; Terashima et al, 2010; Vilar et al, 2006) or neural crest differentiation (e.g., ENC1; Rabadán et al, 2013). Conversely, of the 92 genes reported (Grupenmacher et al, 2013) as over-expressed in RTK relative to AT/RT, 21 were differentially expressed between sub-group 1 and 2, and all were over-expressed in sub-group 2 (one-sided Fisher’s exact p value = 1.193e-13; Table S4).…”

Oroxylin A Induces BDNF Expression on Cortical Neurons through Adenosine A2AReceptor Stimulation: A Possible Role in Neuroprotection

“…A2 A receptor stimulation inhibits primary neurosphere formation and the proliferation of human and rodent neural precursor cells (Scemes et al ., 2003; Stafford et al ., 2007) suggesting that it may play a regulatory role in neuronal differentiation, which is one of the actions of BDNF during developmental period and is well presented in the increase of neurogenesis by oroxylin A (Terashima et al ., 2010; Jeon et al ., 2011; Noble et al ., 2011).…”

Repurposing a pore: highly conserved perforin-like proteins with alternative mechanisms

“…BRINP1 was initially identified as a tumour suppressor protein in human bladder cancer, as part of an effort to locate tumour suppressor genes in bladder cancer cells, and was given the name DBCCR1 (deleted in bladder cancer chromosome region 1) [60,61]. Subsequently, it was observed that ectopically expressing BRINP1 caused cell cycle arrest in cultured cell lines such as bladder cancer cells and the NIH 3T3 cell line [62,63], or even mouse embryonic stem cell-derived neural stem cells [58]. Independently, Kawano et al identified that BRINP1 was predominantly expressed in the central nervous system from early developmental stage to adulthood, and that the expression levels of these proteins were greatly enhanced upon stimulation with bone morphogenetic protein or retinoic acid, from which study the name of the proteins was proposed.…”