Engrailed-2 regulates genes related to vesicle formation and transport in cerebellar Purkinje cells

Mol Cell Neurosci. 2008 Aug;38(4):495-504. doi: 10.1016/j.mcn.2008.04.010. Epub 2008 May 2.

Abstract

Engrailed transcription factors regulate survival, cell fate decisions and axon pathfinding in central neurons. En-2 can also attenuate Purkinje cell (PC) maturation. Here, we use array analysis to scrutinize gene expression in developing PCs overexpressing Engrailed-2 (L7En-2). The majority (70%) of regulated genes was found down-regulated in L7En-2 cerebella, consistent with the known repressive function of Engrailed-2. Differential gene expression, verified by in situ hybridization or Western blotting, was particularly evident during the first postnatal week, when L7En-2 PCs display conspicuous deficits in dendritogenesis. Functional classification revealed clusters of genes linked to vesicle formation and transport. Consistently, Golgi stacks located at the axonal pole of wild type PC somata were rarely detected in L7En-2 PCs. In addition, long continuous stretches of endoplasmic reticulum typically found around the axonal pole of wild type PCs were less frequently observed in transgenic cells. Engrailed-2 might therefore orchestrate PC survival and process formation as a regulator of subcellular organization.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Survival / genetics
  • Cerebellum / cytology
  • Cerebellum / physiology*
  • Down-Regulation / genetics
  • Gene Expression Regulation / physiology
  • Homeodomain Proteins / antagonists & inhibitors
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Protein Transport / genetics
  • Purkinje Cells / cytology
  • Purkinje Cells / physiology*
  • Synaptic Vesicles / genetics*
  • Synaptic Vesicles / metabolism*

Substances

  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • engrailed 2 protein