Hilar granule cells of the mouse dentate gyrus: effects of age, septotemporal location, strain, and selective deletion of the proapoptotic gene BAX.
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.
New York University Langone Medical Center, 227 East 30th Street, 7th Floor, One Park Avenue, New York, NY, 10016, USA. kb1139@nyumc.org.|The Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA. kb1139@nyumc.org.
Keria
http://orcid.org/0000-0002-7737-5797
K
Bermudez-Hernandez
The Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA.
Yi-Ling
YL
Lu
The Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA.
Jillian
J
Moretto
The Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA.
Swati
S
Jain
The Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA.
John J
JJ
LaFrancois
New York University Langone Medical Center, 227 East 30th Street, 7th Floor, One Park Avenue, New York, NY, 10016, USA.|The Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA.
Aine M
AM
Duffy
New York University Langone Medical Center, 227 East 30th Street, 7th Floor, One Park Avenue, New York, NY, 10016, USA.|The Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA.
Helen E
HE
Scharfman
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D064032:Calbindin 2 / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D064231:Nestin / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D013045:Species Specificity; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
D064032:Calbindin 2; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D018398:Homeodomain Proteins; D008869:Microtubule-Associated Proteins; D064231:Nestin; D009479:Neuropeptides; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D000098551:Prospero-Related Homeobox 1 Protein
Adult neurogenesis; Migration; Progenitor; Programmed cell death; Prox1; Stem cell