Reelin and disabled-1 expression in developing and mature human cortical neurons.
In developing mammalian (mouse) brain, Reelin (Reln) is secreted by the Cajal-Retzius (CR) neurons in the marginal zone, binds apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (Vldlr), and induces the phosphorylation of the downstream cytoplasmic molecule disabled-1 (Dab1) in cortical plate neurons. Although this is a well-characterized signaling pathway in mice, it has not been well defined in human brain. In this paper we examined the expression of RELN, APOER2, VLDLR, and DAB1 in the developing human brain by RT-PCR. We further determined the cellular expression of the proteins RELN and DAB1 in 50 human brains ranging in age from 10 gestational weeks (GW) to 62 years using immunochemistry. We found that the pattern of expression of RELN and DAB1 in the human brain isnot identical to that observed in the mouse brain. In particular, we report the novel finding that human DAB1and RELN are coexpressed in CR neurons during cortical development and in cortical pyramidal neurons after neuronal migration is complete. Thus, in the human brain, the whole RELN signaling pathway is present within selected populations of cortical neurons throughout life. We speculate that RELN and DAB1 coexpression in these neurons is necessary for both normal cortical development and mature function.
Deguchi
Kimiko
K
Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
Inoue
Ken
K
Avila
William E
WE
Lopez-Terrada
Dolores
D
Antalffy
Barbara A
BA
Quattrocchi
Carlo C
CC
Sheldon
Michael
M
Mikoshiba
Katsuhiko
K
D'Arcangelo
Gabriella
G
Armstrong
Dawna L
DL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005333:Fetus; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007223:Infant; D007668:Kidney / Q000378:metabolism; D026502:LDL-Receptor Related Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism; D000091042:Reelin Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012697:Serine Endopeptidases
D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D026502:LDL-Receptor Related Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D000091042:Reelin Protein; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases