Interleukin-7 is trophic for embryonic neurons and is expressed in developing brain.
Interleukin-7 (IL7) is a hematopoietic cytokine with critical functions in both B- and T-lymphocyte development. In this study, we find that IL7 exhibits trophic properties in the developing brain as well. Treatment of cultures of embryonic brain with exogenous IL7 increases neuronal survival and results in greater numbers of cells manifesting neurite outgrowth. As demonstrated with single-cell cultures, IL7 acts directly to promote neuronal survival. Expression of the mRNA encoding the high-affinity IL7 receptor (IL7R) is observed in vitro in neurons as well as in subventricular zone progenitor cells. Phosphorylation of p59fyn, which is activated by IL7 in pre-B cells and is thought to be important in neural development, occurs rapidly following IL7 treatment of cultured embryonic neurons. Additionally, the expression of c-myc mRNA, which is modulated by IL7 in lymphoid cells, is upregulated by IL7 in the same CNS cultures. Finally, the messenger RNAs encoding IL7 and IL7R are expressed in vivo in developing brain. The direct neurotrophic properties of IL7 combined with the expression of ligand and receptor in developing brain suggest that IL7 may be a neuronal growth factor of physiological significance during central nervous system (CNS) ontogeny.
Michaelson
M D
MD
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Mehler
M F
MF
Xu
H
H
Gross
R E
RE
Kessler
J A
JA
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D001921:Brain / Q000187:drug effects / Q000196:embryology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D016259:Genes, myc / Q000187:drug effects; D015851:Interleukin-7 / Q000494:pharmacology / Q000502:physiology*; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D012333:RNA, Messenger / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D018123:Receptors, Interleukin / Q000096:biosynthesis; D020395:Receptors, Interleukin-7; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
D015703:Antigens, CD; D015851:Interleukin-7; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7; D017475:Receptors, Nerve Growth Factor; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn