Characterization of neogenin-expressing neural progenitor populations and migrating neuroblasts in the embryonic mouse forebrain.
Many studies have demonstrated a role for netrin-1-deleted in colorectal cancer (DCC) interactions in both axon guidance and neuronal migration. Neogenin, a member of the DCC receptor family, has recently been shown to be a chemorepulsive axon guidance receptor for the repulsive guidance molecule (RGM) family of guidance cues [Rajagopalan S, Deitinghoff L, Davis D, Conrad S, Skutella T, Chedotal A, Mueller B, Strittmatter S (2004) Neogenin mediates the action of repulsive guidance molecule. Nat Cell Biol 6:755-762]. Here we show that neogenin is present on neural progenitors, including neurogenic radial glia, in the embryonic mouse forebrain suggesting that neogenin expression is a hallmark of neural progenitor populations. Neogenin-positive progenitors were isolated from embryonic day 14.5 forebrain using flow cytometry and cultured as neurospheres. Neogenin-positive progenitors gave rise to neurospheres displaying a high proliferative and neurogenic potential. In contrast, neogenin-negative forebrain cells did not produce long-term neurosphere cultures and did not possess a significant neurogenic potential. These observations argue strongly for a role for neogenin in neural progenitor biology. In addition, we also observed neogenin on parvalbumin- and calbindin-positive interneuron neuroblasts that were migrating through the medial and lateral ganglionic eminences, suggesting a role for neogenin in tangential migration. Therefore, neogenin may be a multi-functional receptor regulating both progenitor activity and neuroblast migration in the embryonic forebrain.
Fitzgerald
D P
DP
Queensland Brain Institute, Neural Migration Laboratory, The University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia.
Cole
S J
SJ
Hammond
A
A
Seaman
C
C
Cooper
H M
HM
D000818:Animals; D001757:Blastomeres / Q000502:physiology; D015153:Blotting, Western / Q000379:methods; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D047468:Immunoprecipitation / Q000379:methods; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000502:physiology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology*; D013234:Stem Cells / Q000502:physiology*; D014404:Tubulin / Q000378:metabolism
D027341:Excitatory Amino Acid Transporter 1; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D018809:Proliferating Cell Nuclear Antigen; C493393:Slc1a3 protein, mouse; D014404:Tubulin; C462941:beta3 tubulin, mouse; C091279:neogenin