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Lhx2 regulates the timing of β-catenin-dependent cortical neurogenesis.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2015 Sep 29; Vol. 112 (39), pp. 12199-204. Date of Electronic Publication: 2015 Sep 14. - Publication Year :
- 2015
-
Abstract
- The timing of cortical neurogenesis has a major effect on the size and organization of the mature cortex. The deletion of the LIM-homeodomain transcription factor Lhx2 in cortical progenitors by Nestin-cre leads to a dramatically smaller cortex. Here we report that Lhx2 regulates the cortex size by maintaining the cortical progenitor proliferation and delaying the initiation of neurogenesis. The loss of Lhx2 in cortical progenitors results in precocious radial glia differentiation and a temporal shift of cortical neurogenesis. We further investigated the underlying mechanisms at play and demonstrated that in the absence of Lhx2, the Wnt/β-catenin pathway failed to maintain progenitor proliferation. We developed and applied a mathematical model that reveals how precocious neurogenesis affected cortical surface and thickness. Thus, we concluded that Lhx2 is required for β-catenin function in maintaining cortical progenitor proliferation and controls the timing of cortical neurogenesis.
- Subjects :
- Animals
Computer Simulation
DNA Primers genetics
Galactosides
Gene Expression Regulation, Developmental physiology
HEK293 Cells
Humans
In Situ Hybridization
Indoles
LIM-Homeodomain Proteins genetics
Luciferases
Mice
Mice, Knockout
Real-Time Polymerase Chain Reaction
Transcription Factors genetics
Wnt Signaling Pathway physiology
beta Catenin metabolism
Cerebral Cortex embryology
Gene Expression Regulation, Developmental genetics
LIM-Homeodomain Proteins metabolism
Models, Neurological
Neurogenesis genetics
Neurogenesis physiology
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 112
- Issue :
- 39
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 26371318
- Full Text :
- https://doi.org/10.1073/pnas.1507145112