Sonic hedgehog and BMP2 exert opposing actions on proliferation and differentiation of embryonic neural progenitor cells.
Although Sonic Hedgehog (Shh) plays a critical role in brain development, its actions on neural progenitor cell proliferation and differentiation have not been clearly defined. Transcripts for the putative Shh-receptor genes patched (Ptc) and smoothened (Smo) are expressed by embryonic, postnatal, and adult progenitor cells, suggesting that Shh can act directly on these cells. The recombinant human amino-terminal fragment of Shh protein (Shh-N) alone did not support the survival of cultured progenitor cells, but treatment with Shh-N in the presence of bFGF increased progenitor cell proliferation. Furthermore, treatment of embryonic rat progenitor cells propagated either in primary culture or after mitogen expansion significantly increased the proportions of both beta-tubulin- (neuronal marker) and O4- (oligodendroglial marker) immunoreactive cells and reduced the proportion of nestin- (uncommitted neural progenitor cell marker) immunoreactive cells. By contrast Shh-N had no effect on the elaboration of GFAP- (astroglial marker) immunoreactive cells. Cotreatment with Shh-N and bone morphogenetic protein-2 (BMP2) inhibited the anti-proliferative, astroglial-inductive, and oligodendroglial-suppressive effects of BMP2. Our observations suggest that Shh-N selectively promotes the elaboration of both neuronal and oligodendroglial lineage species and inhibits the effects of BMP2 on progenitor cell proliferation and astroglial differentiation.
Zhu
G
G
Department of Neurology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, 10461, USA. gzhu@aecom.yu.edu
Mehler
M F
MF
Zhao
J
J
Yu Yung
S
S
Kessler
J A
JA
D000375:Aging; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005314:Embryonic and Fetal Development; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D053823:Hedgehog Proteins; D006801:Humans; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D015534:Trans-Activators; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D011506:Proteins; D011994:Recombinant Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D016222:Fibroblast Growth Factor 2