whitesnake/sfpq is required for cell survival and neuronal development in the zebrafish

Abstract

Organogenesis involves both the development of specific cell types and their organization into a functional three-dimensional structure. We are using the zebrafish to assess the genetic basis for brain organogenesis. We show that the whitesnake mutant corresponds to the sfpq (splicing factor, proline/glutamine rich) gene, encoding the PSF protein (polypyrimidine tract-binding protein-associated splicing factor). In vitro studies have shown that PSF is important for RNA splicing and transcription and is a candidate brain-specific splicing factor, however, the in vivo function of this gene is unclear. sfpq is expressed throughout development and in the adult zebrafish, with strong expression in the developing brain, particularly in regions enriched for neuronal progenitors. In the whitesnake mutant, a brain phenotype is visible by 28 hr after fertilization, when it becomes apparent that the midbrain and hindbrain are abnormally shaped. Neural crest, heart, and muscle development or function is also abnormal. sfpq function appears to be required in two distinct phases during development.

Depletion of NEAT1 lncRNA attenuates nucleolar stress by releasing sequestered P54nrb and PSF to facilitate c-Myc translation

“…We hypothesized that some proteins that were normally sequestered by NEAT1 via direct association might be released upon NEAT1 depletion to help cells cope with stress. Indeed, the levels of functional paraspeckle proteins P54nrb and PSF were found to correlate positively with the cell survival [19]. In HeLa cells, depletion of either P54nrb or PSF resulted in the compensatory upregulation of the other paraspeckle proteins (Fig 5A), consistent with the previous observation in P54nrb knockout animals and in patients with mutations in P54nrb [20–22].…”

Zika virus disrupts molecular fingerprinting of human neurospheres

“…ZIKV infection also results in downregulation of a splicing factor, SFPQ, which might result in impairment of neuronal development. In this context, SFPQ is highly expressed in neural progenitors, and required for neuronal migration and differentiation282930. Therefore, it remains to be shown how such differentially regulated targets are advantageous to the virus.…”

Functional and genetic analysis of choroid plexus development in zebrafish

“…Because none of our choroid plexus mutants exhibited a phenotype at 24 hpf, we did not expect to see defects in midline separation as described in Lowery et al (2009). Choroid plexus mutants such as cp79.6 and cp140.2 have a brain ventricle that closely resembles normal larvae at 2 dpf (Lowery et al, 2007), indicating these mutants may have a developmental delay and not necessarily a brain ventricle defect. Also, cp140.2 mutants at 3 dpf are similar to wild-type larvae at 2 dpf in that the fluorescein accumulated within the brain ventricle rather than concentrating within choroid plexus epithelium as it does normally on day 3.…”