Pparα deficiency inhibits the proliferation of neuronal and glial precursors in the zebrafish central nervous system

Abstract

Background: Many molecules and signaling pathways involved in neural development play a role in neurodegenerative diseases and brain tumor progression. Peroxisome proliferator‐activated receptor (PPAR) proteins regulate the differentiation of tissues and the progression of many diseases. However, the role of these proteins in neural development is unclear. Results: We examined the function of Pparα in the neural development of zebrafish. Two duplicate paralogs for mammalian PPARA/Ppara, namely pparaa and pparab, are present in the zebrafish genome. Both pparaa and pparab are expressed in the developing central nervous system in zebrafish embryos. Inhibiting the function of Pparα by using either the PPARα/Pparα antagonist GW6471 or pparaa or pparab truncated constructs produced identical phenotypes, which were sufficient to reduce the proliferation of neuronal and glial precursor cells without affecting the formation of neural progenitors. Conclusions: We demonstrated that both Pparαa and Pparαb proteins are essential regulators of the proliferation of neuronal and glial precursors. This study provides a better understanding of the functions of PPARα/Pparα in neural development and further expands our knowledge of the potential role of PPARα/Pparα in neurological disorders and brain tumors. Developmental Dynamics 247:1264–1275, 2018. © 2018 Wiley Periodicals, Inc.

Peroxisomal proliferator‐activated receptor α‐b deficiency induces the reprogramming of nutrient metabolism in zebrafish

“…The zebrafish (Danio rerio) has been regarded as a well-accepted animal model and widely used in the studies of cellular energy metabolism (Den Broeder et al 2015;Li et al 2017;Yang et al 2017;Yang et al 2018;Lu et al 2019). Two paralogues of PPARα have been defined in zebrafish on the basis of their similarity: pparaa (GenBank: NM 0 011 61333.1) and pparab (GenBank: NM 0 011 02567.1) (Hsieh et al 2018). We found that zebrafish predominantly express the pparab subtype.…”

“…Two paralogues of PPARα have been defined in zebrafish on the basis of their similarity: pparaa (GenBank: NM_0 011 61333.1) and pparab (GenBank: NM_0 011 02567.1) (Hsieh et al . 2018). We found that zebrafish predominantly express the pparab subtype.…”

Trim46 contributes to the midbrain development via Sonic Hedgehog signaling pathway in zebrafish embryos

“…Two duplicate paralogs of mammalian PPARA namely, Pparαa and Pparαb are present in the zebrafish genome. Both Pparαa and Pparαb are essential regulators of the proliferation of neuronal and glial precursors in zebrafish embryos (Hsieh et al 2018). Based on our findings that trim46a is implicated in zebrafish neurogenesis, further study of its relevance to Pparαa and Pparαb would be an interesting topic.…”

Peroxisome proliferator-activated receptor α as a novel therapeutic target for schizophrenia

“…S5a and b). The orthologs of mammalian PPARα regulate the formation of neurons and glial cells in the zebrafish [74] . In vitro studies showed that PPARα is expressed in neural stem cells, and that some PPARα target genes modulate cell proliferation [ 22 , 75 ].…”