Identification of the mammalian homolog of the splicing regulator Suppressor-of-white-apricot as a thyroid hormone regulated gene

  • Cuadrado A
  • Bernal J
  • Muñoz A
  • 4

    Readers

    Mendeley users who have this article in their library.
  • 17

    Citations

    Citations of this article.

Abstract

Mammalian brain development is controlled by thyroid hormone through the regulation of target genes. In this study, we describe for the first time that a splicing regulator gene is under thyroid hormone control in the rat brain during the critical period of neuronal differentiation. By differential display, we have identified the mammalian homolog of the Drosophila splicing regulator Suppressor-of-white-apricot (SWAP) as a thyroid hormone-regulated gene in an immortal line of rat neuroblasts, E18 cells. Using Northern blotting and in situ hybridization, we found that expression of SWAP is under thyroid control in the developing rat brain. SWAP gene expression is highest during the first 10 days of life (P0-P10), preferentially in cerebral cortex, cerebellum, subventricular epithelium, pirifom cortex, hippocampus, amygdala, and caudate putamen. At later stages (P15-P30) SWAP expression decreases, being detectable only in the cerebellum, hippocampus, and layers II/III of cerebral and piriform cortexes. We found that hypothyroidism causes an abnormal high level of SWAP RNA expression at P5-P15 throughout the brain except the cerebellum. Significantly, thyroid hormone treatment in vivo of hypothyroid animals led to a normalization of SWAP RNA expression. Furthermore, similar hormone treatment caused a decrease in SWAP expression in control rats. By modulating the expression of SWAP and perhaps other splicing regulators thyroid hormone may exert wide regulatory effects on multiple genes. The regulation of SWAP gene defines a novel mechanism of action of thyroid hormone which can be important for its effects in the developing brain.

Author-supplied keywords

  • Differential display
  • Gene regulation
  • SWAP gene
  • Splicing
  • Thyroid hormone

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Ana Cuadrado

  • Juan Bernal

  • Alberto Muñoz

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free