Abstract
An important feature of the cerebral cortex is its layered organization, which is modulated in an area-specific manner. We found that the transcription factor AP2gamma regulates laminar fate in a region-specific manner. Deletion of AP2gamma (also known as Tcfap2c) during development resulted in a specific reduction of upper layer neurons in the occipital cortex, leading to impaired function and enhanced plasticity of the adult visual cortex. AP2gamma functions in apical progenitors, and its absence resulted in mis-specification of basal progenitors in the occipital cortex at the time at which upper layer neurons were generated. AP2gamma directly regulated the basal progenitor fate determinants Math3 (also known as Neurod4) and Tbr2, and its overexpression promoted the generation of layer II/III neurons in a time- and region-specific manner. Thus, AP2gamma acts as a regulator of basal progenitor fate, linking regional and laminar specification in the mouse developing cerebral cortex.
MeSH terms
-
Adult
-
Animals
-
Bromodeoxyuridine / metabolism
-
Cell Count / methods
-
Cell Differentiation / physiology*
-
Cell Line, Transformed
-
Cerebral Cortex* / cytology
-
Cerebral Cortex* / embryology
-
Cerebral Cortex* / growth & development
-
Embryo, Mammalian
-
Embryonic Stem Cells / physiology*
-
Evoked Potentials, Visual / genetics
-
Evoked Potentials, Visual / physiology
-
Eye Proteins / genetics
-
Eye Proteins / metabolism
-
Fetus
-
Gene Deletion
-
Gene Expression Regulation, Developmental / genetics
-
Gene Expression Regulation, Developmental / physiology
-
Green Fluorescent Proteins / genetics
-
Homeodomain Proteins / genetics
-
Homeodomain Proteins / metabolism
-
Humans
-
Immediate-Early Proteins / genetics
-
Ki-67 Antigen / metabolism
-
Macaca fascicularis
-
Mice
-
Mice, Inbred C57BL
-
Mice, Transgenic
-
Neurogenesis / physiology*
-
PAX6 Transcription Factor
-
Paired Box Transcription Factors / genetics
-
Paired Box Transcription Factors / metabolism
-
Photic Stimulation / methods
-
RNA, Messenger / metabolism
-
Repressor Proteins / genetics
-
Repressor Proteins / metabolism
-
T-Box Domain Proteins / metabolism
-
Transcription Factor AP-2 / genetics
-
Transcription Factor AP-2 / physiology*
-
Transcription Factors / genetics
-
Transfection / methods
-
Tumor Suppressor Proteins / genetics
Substances
-
Btg2 protein, mouse
-
Eomes protein, mouse
-
Eye Proteins
-
Homeodomain Proteins
-
Immediate-Early Proteins
-
Ki-67 Antigen
-
PAX6 Transcription Factor
-
PAX6 protein, human
-
Paired Box Transcription Factors
-
Pax6 protein, mouse
-
RNA, Messenger
-
Repressor Proteins
-
T-Box Domain Proteins
-
Transcription Factor AP-2
-
Transcription Factors
-
Tumor Suppressor Proteins
-
empty spiracles homeobox proteins
-
Green Fluorescent Proteins
-
Bromodeoxyuridine