COUP-TFI regulates the balance of cortical patterning between frontal/motor and sensory areas.
We used cortex-specific deletion of the transcription factor gene COUP-TFI (also known as Nr2f1) in mice to demonstrate previously unknown fundamental roles for it in patterning mammalian neocortex into areas. The highest COUP-TFI expression is observed in the cortical progenitors and progeny in parietal and occipital cortex that form sensory areas, and the lowest expression was observed in frontal cortex that includes motor areas. Cortical deletion of COUP-TFI resulted in massive expansion of frontal areas, including motor, to occupy most of neocortex, paralleled by marked compression of sensory areas to caudal occipital cortex. These area patterning changes are preceded and paralleled by corresponding changes in molecular markers of area identity and altered axonal projections to maintain patterned area-specific input and output connections. We conclude that COUP-TFI is required for balancing patterning of neocortex into frontal/motor and sensory areas by acting in its expression domain to repress frontal/motor area identities and to specify sensory area identities.
Armentano
Maria
M
Telethon Institute of Genetics and Medicine (TIGEM), Developmental Disorders Program, Via P. Castellino 111, 80131 Naples, Italy.
Chou
Shen-Ju
SJ
Tomassy
Giulio Srubek
GS
Leingärtner
Axel
A
O'Leary
Dennis D M
DD
Studer
Michèle
M
D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D051838:COUP Transcription Factor I / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009044:Motor Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051762:PAX2 Transcription Factor / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013003:Somatosensory Cortex / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000099260:Empty Spiracles Homeobox Proteins