Expression of insulin-like growth factor system genes during the early postnatal neurogenesis in the mouse hippocampus.
Insulin-like growth factor-1 (IGF-1) is essential to hippocampal neurogenesis and the neuronal response to hypoxia/ischemia injury. IGF (IGF-1 and -2) signaling is mediated primarily by the type 1 IGF receptor (IGF-1R) and modulated by six high-affinity binding proteins (IGFBP) and the type 2 IGF receptor (IGF-2R), collectively termed IGF system proteins. Defining the precise cells that express each is essential to understanding their roles. With the exception of IGFBP-1, we found that mouse hippocampus expresses mRNA for each of these proteins during the first 2 weeks of postnatal life. Compared to postnatal day 14 (P14), mRNA abundance at P5 was higher for IGF-1, IGFBP-2, -3, and -5 (by 71%, 108%, 100%, and 98%, respectively), lower for IGF-2, IGF-2R, and IGFBP-6 (by 65%, 78%, and 44%, respectively), and unchanged for IGF-1R and IGFBP-4. Using laser capture microdissection (LCM), we found that granule neurons and pyramidal neurons exhibited identical patterns of expression of IGF-1, IGF-1R, IGF-2R, IGFBP-2, and -4, but did not express other IGF system genes. We then compared IGF system expression in mature granule neurons and their progenitors. Progenitors exhibited higher mRNA levels of IGF-1 and IGF-1R (by 130% and 86%, respectively), lower levels of IGF-2R (by 72%), and similar levels of IGFBP-4. Our data support a role for IGF in hippocampal neurogenesis and provide evidence that IGF actions are regulated within a defined in vivo milieu.
Zhang
Jihui
J
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7039, USA.
Moats-Staats
Billie M
BM
Ye
Ping
P
D'Ercole
A Joseph
AJ
D000818:Animals; D000831:Animals, Newborn; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D007834:Lasers; D051379:Mice; D008810:Mice, Inbred C57BL; D042282:Microdissection; D009474:Neurons / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism
D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D017526:Receptor, IGF Type 1