Hilar granule cells of the mouse dentate gyrus: effects of age, septotemporal location, strain, and selective deletion of the proapoptotic gene BAX

Brain Struct Funct. 2017 Sep;222(7):3147-3161. doi: 10.1007/s00429-017-1391-5. Epub 2017 Mar 17.

Abstract

The dentate gyrus (DG) principal cells are glutamatergic granule cells (GCs), and they are located in a compact cell layer. However, GCs are also present in the adjacent hilar region, but have been described in only a few studies. Therefore, we used the transcription factor prospero homeobox 1 (Prox1) to quantify GCs at postnatal day (PND) 16, 30, and 60 in a common mouse strain, C57BL/6J mice. At PND16, there was a large population of Prox1-immunoreactive (ir) hilar cells, with more in the septal than temporal hippocampus. At PND30 and 60, the size of the hilar Prox1-ir cell population was reduced. Similar numbers of hilar Prox1-expressing cells were observed in PND30 and 60 Swiss Webster mice. Prox1 is usually considered to be a marker of postmitotic GCs. However, many Prox1-ir hilar cells, especially at PND16, were not double-labeled with NeuN, a marker typically found in mature neurons. Most hilar Prox1-positive cells at PND16 co-expressed doublecortin (DCX) and calretinin, markers of immature GCs. Double-labeling with a marker of actively dividing cells, Ki67, was not detected. These results suggest that, surprisingly, a large population of cells in the hilus at PND16 are immature GCs (Type 2b and Type 3 cells). We also asked whether hilar Prox1-ir cell numbers are modifiable. To examine this issue, we conditionally deleted the proapoptotic gene BAX in Nestin-expressing cells at a time when there are numerous immature GCs in the hilus, PND2-8. When these mice were examined at PND60, the numbers of Prox1-ir hilar cells were significantly increased compared to control mice. However, deletion of BAX did not appear to change the proportion that co-expressed NeuN, suggesting that the size of the hilar Prox1-expressing population is modifiable. However, deleting BAX, a major developmental disruption, does not appear to change the proportion that ultimately becomes neurons.

Keywords: Adult neurogenesis; Migration; Progenitor; Programmed cell death; Prox1; Stem cell.

MeSH terms

  • Aging / physiology*
  • Animals
  • Animals, Newborn
  • Calbindin 2 / metabolism
  • Dentate Gyrus / cytology*
  • Gene Expression Regulation, Developmental / genetics*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Nestin / genetics
  • Nestin / metabolism*
  • Neurogenesis / genetics
  • Neurons / metabolism*
  • Neuropeptides / metabolism
  • Species Specificity
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • bcl-2-Associated X Protein / deficiency*
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Calbindin 2
  • Homeodomain Proteins
  • Microtubule-Associated Proteins
  • Nestin
  • Neuropeptides
  • Tumor Suppressor Proteins
  • bcl-2-Associated X Protein
  • doublecortin protein
  • prospero-related homeobox 1 protein