COUP-TFI coordinates cortical patterning, neurogenesis, and laminar fate and modulates MAPK/ERK, AKT, and beta-catenin signaling.
A major unsolved question in cortical development is how proliferation, neurogenesis, regional growth, regional identity, and laminar fate specification are coordinated. Here we provide evidence, using loss-of-function and gain-of-function manipulations, that the COUP-TFI orphan nuclear receptor promotes ventral cortical fate, promotes cell cycle exit and neural differentiation, regulates the balance of early- and late-born neurons, and regulates the balanced production of different types of layer V cortical projection neurons. We suggest that COUP-TFI controls these processes by repressing Mapk/Erk, Akt, and beta-catenin signaling.
Faedo
Andrea
A
Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco, CA 94158, USA. andrea.faedo@ucsf.edu
Tomassy
Giulio Srubek
GS
Ruan
Youlin
Y
Teichmann
Hannah
H
Krauss
Stefan
S
Pleasure
Samuel J
SJ
Tsai
Sophia Y
SY
Tsai
Ming-Jer
MJ
Studer
Michèle
M
Rubenstein
John L R
JL
D000818:Animals; D051838:COUP Transcription Factor I / Q000235:genetics* / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019579:Neocortex / Q000166:cytology / Q000196:embryology* / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism*
D051838:COUP Transcription Factor I; C495267:CTNNB1 protein, mouse; D051176:beta Catenin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases