Tbr1 regulates differentiation of the preplate and layer 6.
During corticogenesis, early-born neurons of the preplate and layer 6 are important for guiding subsequent neuronal migrations and axonal projections. Tbr1 is a putative transcription factor that is highly expressed in glutamatergic early-born cortical neurons. In Tbr1-deficient mice, these early-born neurons had molecular and functional defects. Cajal-Retzius cells expressed decreased levels of Reelin, resulting in a reeler-like cortical migration disorder. Impaired subplate differentiation was associated with ectopic projection of thalamocortical fibers into the basal telencephalon. Layer 6 defects contributed to errors in the thalamocortical, corticothalamic, and callosal projections. These results show that Tbr1 is a common genetic determinant for the differentiation of early-born glutamatergic neocortical neurons and provide insights into the functions of these neurons as regulators of cortical development.
Hevner
R F
RF
Nina Ireland Laboratory of, Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA.
Shi
L
L
Justice
N
N
Hsueh
Y
Y
Sheng
M
M
Smiga
S
S
Bulfone
A
A
Goffinet
A M
AM
Campagnoni
A T
AT
Rubenstein
J L
JL
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D016923:Cell Death; D002465:Cell Movement / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005855:Germ Layers / Q000378:metabolism*; D007763:Lac Operon / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009154:Mutation; D019579:Neocortex / Q000002:abnormalities / Q000196:embryology* / Q000254:growth & development; D009419:Nerve Tissue Proteins; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D009435:Synaptic Transmission; D020825:T-Box Domain Proteins
D015816:Cell Adhesion Molecules, Neuronal; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D020825:T-Box Domain Proteins; C492271:Tbr1 protein, mouse; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases