Developmental expression of the cell cycle and apoptosis controlling gene, Lot1, in the rat cerebellum and in cultures of cerebellar granule cells

Brain Res Dev Brain Res. 2003 May 14;142(2):193-202. doi: 10.1016/s0165-3806(03)00092-0.


The Lot1 gene encodes a zinc finger protein that, in vitro, concurrently regulates apoptosis and cell cycle arrest and belongs to a recently identified family of proteins with oncogenic and tumor-supressor functions. The present study, based on the development of the first antibody reportedly produced against rat Lot1, examines protein expression during normal development of the rat cerebellum and following methylazoxymethanol (MAM) administration, which results in hypoplasia of the cerebellar granule cell population. Using light microscopic immunocytochemistry, specific immunostaining for the Lot1 protein was observed at postnatal days 2 to 7 in the superficial external granule layer composed primarily of proliferating neuronal precursor cells. Purkinje cells showed distinct nuclear labeling at P7. In the adult cerebellum, the overall low Lot1 level was essentially associated with Purkinje cells. Experimentally altered developmental conditions, such as those obtained through MAM-induced microencephaly, did not drastically affect the pattern of Lot1 expression. In particular, Purkinje cells continued to show normal levels of immunoreactivity notwithstanding the altered cerebellar architecture. Primary cultures of cerebellar granule cells showed a temporal pattern of Lot1 expression resembling that of in vivo development, with mRNA and protein levels progressively decreasing with differentiation. When cerebellar granule cells were exposed to different neurotoxic challenges, Lot1 appeared not affected by purely apoptotic cell death, while transitorily induced by mixed necrotic-apoptotic cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Cerebellum / abnormalities*
  • Cerebellum / cytology
  • Cerebellum / growth & development*
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / genetics
  • Genes, Tumor Suppressor
  • Methylazoxymethanol Acetate / analogs & derivatives*
  • Methylazoxymethanol Acetate / pharmacology
  • Nervous System Malformations / chemically induced
  • Nervous System Malformations / genetics
  • Nervous System Malformations / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurotoxins / pharmacology
  • Purkinje Cells / cytology
  • Purkinje Cells / drug effects
  • Purkinje Cells / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Cell Cycle Proteins
  • Neurotoxins
  • Plagl1 protein, rat
  • RNA, Messenger
  • Transcription Factors
  • Methylazoxymethanol Acetate
  • methylazoxymethanol