Bone morphogenetic proteins produced by cells within embryoid bodies inhibit ventral directed differentiation by Sonic Hedgehog.
Mouse embryoid bodies (EBs) differentiate into dorsal spinal cord neural progenitors in response to retinoic acid (RA). Our data demonstrate that the addition of Sonic Hedgehog (Shh) directs towards a ventral spinal cord neural tube fate, but only at extremely high concentrations. One possible explanation is the presence of dorsal directing factors. Bone morphogenetic proteins (BMPs), known to direct dorsal spinal cord neural differentiation, were expressed in RA-treated EBs. Shh more potently directed ventral differentiation when combined with the BMP inhibitor Noggin. Further, when BMP7 was added, the ability of Shh to direct ventral differentiation was further mitigated.
Institute for Cell Engineering, BRB 772, 733 North Broadway, Baltimore, MD 21205, USA. jsternec@jhmi.edu
Jared L
JL
Sterneckert
Christine M
CM
Hill
Richard
R
Palmer
John D
JD
Gearhart
D000818:Animals; D019521:Body Patterning; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D046508:Culture Techniques; D004622:Embryo, Mammalian / Q000166:cytology*; D004627:Embryonic Induction; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D008938:Mitosis; D009474:Neurons / Q000166:cytology; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000196:embryology; D013234:Stem Cells / Q000166:cytology; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology; D029961:Zebrafish Proteins; D000099176:Noggin Protein
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D053823:Hedgehog Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D014212:Tretinoin; D029961:Zebrafish Proteins; D000099176:Noggin Protein