FGF8 signaling patterns the telencephalic midline by regulating putative key factors of midline development.
FGF8 has been reported to act as a primary regulator of neocortical patterning along the anteroposterior (AP) axis in the mouse telencephalon, and disruption of FGF signaling causes distortion of molecular arealization along the AP axis. Since hypoplasia of midline structures is observed in Fgf8 mutant mice, FGF8 is also postulated to be involved in telencephalic midline development. In this study we analyzed the role of FGF8 in midline development by means of gain-of-function and loss-of-function experiments. The results showed that FGF8 up-regulates the expression of transcription factor (TF) genes, including putative key factors involved in midline development. Although FGF8 had been thought to act downstream of SHH signaling, ectopic FGF8 up-regulates the expression of midline TF genes in Shh null mice, suggesting that FGF signaling acts as an upstream positive regulator of midline TFs during midline development independently of SHH.
Okada
Toshiaki
T
Laboratory for Cell Culture Development, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan. toshiokada@brain.riken.jp
Okumura
Yuki
Y
Motoyama
Jun
J
Ogawa
Masaharu
M
D000818:Animals; D019521:Body Patterning; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008813:Mice, Inbred ICR; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013687:Telencephalon / Q000196:embryology* / Q000378:metabolism; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics; D000074290:Zinc Finger Protein Gli3
C496457:Fgf8 protein, mouse; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D060850:LIM-Homeodomain Proteins; C102995:Lhx5 protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C465570:Shh protein, mouse; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; C491811:Zic2 protein, mouse; D000074290:Zinc Finger Protein Gli3; D051524:Fibroblast Growth Factor 8