Secretoneurin A regulates neurogenic and inflammatory transcriptional networks in goldfish (Carassius auratus) radial glia

Abstract

Radial glial cells (RGCs) are the most abundant macroglia in the teleost brain and have established roles in neurogenesis and neurosteroidogenesis; however, their transcriptome remains uncharacterized, which limits functional understanding of this important cell type. Using cultured goldfish RGCs, RNA sequencing and de novo transcriptome assembly were performed, generating the first reference transcriptome for fish RGCs with 17,620 unique genes identified. These data revealed that RGCs express a diverse repertoire of receptors and signaling molecules, suggesting that RGCs may respond to and synthesize an array of hormones, peptides, cytokines, and growth factors. Building upon neuroanatomical data and studies investigating direct neuronal regulation of RGC physiology, differential gene expression analysis was conducted to identify transcriptional networks that are responsive to the conserved secretogranin II-derived neuropeptide secretoneurin A (SNa). Pathway analysis of the transcriptome indicated that cellular processes related to the central nervous system (e.g., neurogenesis, synaptic plasticity, glial cell development) and immune functions (e.g., immune system activation, leukocyte function, macrophage response) were preferentially modulated by SNa. These data reveal an array of new functions that are proposed to be critical to neuronal-glial interactions through the mediator SNa.

Steroid Transport, Local Synthesis, and Signaling within the Brain: Roles in Neurogenesis, Neuroprotection, and Sexual Behaviors

“…In contrast, immunohistochemistry on cyp19a1b -GFP transgenic zebrafish clearly showed Pgr-expressing cells along the ventricle correspond to AroB + RGCs (Diotel et al, 2011c ). These data were confirmed by a transcriptomic analysis showing pgr mRNA expression in cultured goldfish RGCs (Da Fonte et al, 2017 ). Pgr expression is consequently high in the estrogen-synthesizing RGCs.…”

“…In addition, expression of cyp21a2, cyp11c1 , and fdx1/fdx1b (co-factors of glucocorticoid synthesis) was recently described in adult zebrafish brain (Weger et al, accepted ), and patterns appeared similar to other steroidogenic enzymes. Furthermore, isolation and culture of goldfish RGCs was performed (Xing et al, 2014 ), and deep RNA sequencing of these RGCs indicates expression of steroidogenic acute regulatory protein ( star ), cyp11a1, cyp17a1, fdx1, hsd17b10 in addition to cyp19a1b and 5 α -reductase (Da Fonte et al, 2017 ). Proteomic analyses also revealed the production of 20β-Hsd (Xing et al, 2016 ).…”

“…However, esr2b was recently shown to be expressed in AroB-expressing RGCs (Pellegrini et al, 2015 ), and RT-PCR analysis performed in glial cells enriched cultures from adult trout or goldfish suggested that a weak expression of ERα could not be excluded (Menuet et al, 2003 ; Xing et al, 2015 ). A recent study designed to characterize the transcriptome of cultured goldfish RGCs and reported esr1, esr2b , and esr2a expression in these neural progenitors (Da Fonte et al, 2017 ).…”

“…Originally, it was proposed that goldfish RGCs did not express the G-protein coupled estrogen receptor because attempts to amplify a specific cDNA from cultured cells failed (Xing et al, 2015 ). However, whole RNA sequencing of separate primary cultures of these cells revealed expression of gper1 , suggesting that some subpopulations of RGCs express the membrane ER (Da Fonte et al, 2017 ).…”

“…All neuroanatomical studies undertaken to date show that ARs are expressed in ventricular margins, where RGC are located (Harbott et al, 2007 ; Gorelick et al, 2008 ; Forlano et al, 2010 ; Pouso et al, 2010 ). Recently, transcriptomic analysis showed the expression of ar in goldfish RGCs (Da Fonte et al, 2017 ).…”