Prickle1 is expressed in distinct cell populations of the central nervous system and contributes to neuronal morphogenesis

Hum Mol Genet. 2013 Jun 1;22(11):2234-46. doi: 10.1093/hmg/ddt075. Epub 2013 Feb 18.

Abstract

Development of axons and dendrites constitutes a critical event in neuronal maturation and seems to require signaling through the planar cell polarity (PCP) pathway. Mutations in components of the PCP pathway lead to a spectrum of neurological phenotypes and disorders. For example, a missense mutation in Prickle 1 (Pk1) is associated with progressive myoclonus epilepsy (PME) in humans, and its reduced gene dosage increases sensitivity to induced seizure in mice. In an effort to unravel the role of the PCP pathway in mammalian neuronal development, we examined the expression of Pk1 in the central nervous system (CNS) using in situ hybridization (ISH) in combination with a genetic knock-in approach. We show that Pk1 transcripts are detected in the postmitotic cells of the subplate and cortical plate during mid- and late stages of cortical neurogenesis. In adult brain, Pk1 is expressed in distinct neuronal and glial cell populations, with dynamic formation of dendrites and glial processes during development. Of all the cell types in the mature retina, the highest expression of Pk1 is detected in cholinergic amacrine neurons. Knockdown of Pk1 by shRNA or dominant-negative constructs causes reduced axonal and dendritic extension in hippocampal neurons. Similarly, Pk1 knockdown in neonatal retina leads to defects in inner and outer segments and axon terminals of photoreceptors. Our studies implicate Pk1 function in axonal-dendritic development associated with the maturation of CNS neurons.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Brain / embryology
  • Brain / metabolism
  • Central Nervous System / embryology*
  • Central Nervous System / metabolism*
  • Dendrites / metabolism
  • Gene Expression Regulation, Developmental*
  • Gene Knock-In Techniques
  • Gene Knockdown Techniques
  • Genes, Reporter
  • Hippocampus / metabolism
  • Humans
  • LIM Domain Proteins / genetics*
  • LIM Domain Proteins / metabolism
  • Mice
  • Morphogenesis / genetics*
  • Neurogenesis / genetics*
  • Neurons / metabolism
  • Retina / embryology
  • Retina / metabolism
  • Retinal Rod Photoreceptor Cells / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • LIM Domain Proteins
  • Prickle1 protein, mouse