Distinct regulators control the expression of the mid-hindbrain organizer signal FGF8.
Local expression of FGF8 at the mid/hindbrain boundary (MHB) governs the development of multiple neurons and support cells. Here we show that the paired-domain protein Pax2 is necessary and sufficient for the induction of FGF8 in part by regulating the expression of Pax5&8. A network of transcription and secreted factors, including En1, Otx2, Gbx2, Grg4 and Wnt1&4, that is established independently of Pax2, further refines the expression domain and level of FGF8 at the MHB through opposing effects on Pax2 activity. Our results indicate that the expression of local organizing factors is controlled by combinatorial interaction between inductive and modulatory factors.
Ye
W
W
Department of Molecular Biology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA.
Bouchard
M
M
Stone
D
D
Liu
X
X
Vella
F
F
Lee
J
J
Nakamura
H
H
Ang
S L
SL
Busslinger
M
M
Rosenthal
A
A
D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D004627:Embryonic Induction / Q000235:genetics*; D005333:Fetus; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins; D051857:Otx Transcription Factors; D051762:PAX2 Transcription Factor; D051757:PAX5 Transcription Factor; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
D004268:DNA-Binding Proteins; C513076:EN1 protein, human; C080330:En1 protein, mouse; C496457:Fgf8 protein, mouse; C513182:Gbx2 protein, mouse; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D051762:PAX2 Transcription Factor; D051757:PAX5 Transcription Factor; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C497319:Pax2 protein, mouse; C497282:Pax5 protein, mouse; C499496:Pax8 protein, mouse; C494467:Pax8 protein, zebrafish; D011506:Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D029961:Zebrafish Proteins; C513181:gbx2 protein, zebrafish; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors