Patterning of the dorsal telencephalon and cerebral cortex by a roof plate-Lhx2 pathway.
The organizing centers and molecules that pattern the cerebral cortex have been elusive. Here we show that cortical patterning involves regulation of the Lhx2 homeobox gene by the roof plate. Roof plate ablation results in reduced cortical size and Lhx2 expression defects that implicate roof plate signals in the bimodal regulation of Lhx2 in vivo. Bimodal Lhx2 regulation can be recapitulated in explants using two roof plate-derived signaling molecules, Bmp4 and Bmp2. Loss of Lhx2 function results in profound losses of cortical progenitors and neurons, but Lhx2 mutants continue to generate cortical neurons from dorsal sources that may include the roof plate region itself. These findings provide evidence for the roof plate as an organizing center of the developing cortex and for a roof plate-Lhx2 pathway in cortical patterning.
Monuki
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ES
Division of Neurogenetics, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
Porter
F D
FD
Walsh
C A
CA
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055412:Growth Differentiation Factors; D006133:Growth Substances / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000502:physiology; D011247:Pregnancy; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D016212:Transforming Growth Factor beta
C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; C499471:Gdf7 protein, mouse; D055412:Growth Differentiation Factors; D006133:Growth Substances; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C489784:Lhx2 protein, mouse; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C086559:growth differentiation factor 7