CBF1 controls the retinotectal topographical map along the anteroposterior axis through multiple mechanisms.
Chick brain factor 1 (CBF1), a nasal retina-specific winged-helix transcription factor, is known to prescribe the nasal specificity that leads to the formation of the precise retinotectal map, especially along the anteroposterior (AP) axis. However, its downstream topographic genes and the molecular mechanisms by which CBF1 controls the expression of them have not been elucidated. We show that misexpression of CBF1 represses the expression of EphA3 and CBF2, and induces that of SOHo1, GH6, ephrin A2 and ephrin A5. CBF1 controls ephrin A5 by a DNA binding-dependent mechanism, ephrin A2 by a DNA binding-independent mechanism, and CBF2, SOHo1, GH6 and EphA3 by dual mechanisms. BMP2 expression begins double-gradiently in the retina from E5 in a complementary pattern to Ventroptin expression. Ventroptin antagonizes BMP2 as well as BMP4. CBF1 interferes in BMP2 signaling and thereby induces expression of ephrin A2. Our data suggest that CBF1 is located at the top of the gene cascade for the regional specification along the nasotemporal (NT) axis in the retina and distinct BMP signals play pivotal roles in the topographic projection along both axes.
Takahashi
Hiroo
H
Division of Molecular Neurobiology, National Institute for Basic Biology, Graduate University for Advanced Studies, Okazaki 444-8585, Japan.
Shintani
Takafumi
T
Sakuta
Hiraki
H
Noda
Masaharu
M
D000344:Afferent Pathways; D000818:Animals; D030161:Avian Proteins; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002633:Chemotaxis / Q000502:physiology; D002642:Chick Embryo; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D036383:Ephrin-A2 / Q000235:genetics / Q000378:metabolism; D036384:Ephrin-A3 / Q000235:genetics / Q000378:metabolism; D036386:Ephrin-A5 / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013477:Superior Colliculi / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D019076:Transgenes; D014764:Viral Proteins
D030161:Avian Proteins; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D036383:Ephrin-A2; D036384:Ephrin-A3; D036386:Ephrin-A5; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C085723:SOHO-1 protein, Gallus gallus; D014764:Viral Proteins; C490425:v-qin protein, Avian sarcoma virus 31; D004247:DNA