Lhx2 selector activity specifies cortical identity and suppresses hippocampal organizer fate.
The earliest step in creating the cerebral cortex is the specification of neuroepithelium to a cortical fate. Using mouse genetic mosaics and timed inactivations, we demonstrated that Lhx2 acts as a classic selector gene and essential intrinsic determinant of cortical identity. Lhx2 selector activity is restricted to an early critical period when stem cells comprise the cortical neuroepithelium, where it acts cell-autonomously to specify cortical identity and suppress alternative fates in a spatially dependent manner. Laterally, Lhx2 null cells adopt antihem identity, whereas medially they become cortical hem cells, which can induce and organize ectopic hippocampal fields. In addition to providing functional evidence for Lhx2 selector activity, these findings show that the cortical hem is a hippocampal organizer.
Mangale
Vishakha S
VS
Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
Hirokawa
Karla E
KE
Satyaki
Prasad R V
PR
Gokulchandran
Nandini
N
Chikbire
Satyadeep
S
Subramanian
Lakshmi
L
Shetty
Ashwin S
AS
Martynoga
Ben
B
Paul
Jolly
J
Mai
Mark V
MV
Li
Yuqing
Y
Flanagan
Lisa A
LA
Tole
Shubha
S
Monuki
Edwin S
ES
D000818:Animals; D002449:Cell Aggregation; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002678:Chimera; D018891:Dentate Gyrus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D004627:Embryonic Induction; D053595:Embryonic Stem Cells / Q000378:metabolism; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000166:cytology / Q000196:embryology*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D046569:Neuroepithelial Cells / Q000166:cytology / Q000378:metabolism; D020897:Organizers, Embryonic / Q000196:embryology / Q000502:physiology*; D016548:Prosencephalon / Q000196:embryology / Q000378:metabolism; D017966:Pyramidal Cells / Q000166:cytology / Q000196:embryology; D011995:Recombination, Genetic; D013687:Telencephalon / Q000166:cytology / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C489784:Lhx2 protein, mouse; D014157:Transcription Factors