Dlx5 and Dlx6 regulate the development of parvalbumin-expressing cortical interneurons.
Dlx5 and Dlx6 homeobox genes are expressed in developing and mature cortical interneurons. Simultaneous deletion of Dlx5 and 6 results in exencephaly of the anterior brain; despite this defect, prenatal basal ganglia differentiation appeared largely intact, while tangential migration of Lhx6(+) and Mafb(+) interneurons to the cortex was reduced and disordered. The migration deficits were associated with reduced CXCR4 expression. Transplantation of mutant immature interneurons into a wild-type brain demonstrated that loss of either Dlx5 or Dlx5&6 preferentially reduced the number of mature parvalbumin(+) interneurons; those parvalbumin(+) interneurons that were present had increased dendritic branching. Dlx5/6(+/-) mice, which appear normal histologically, show spontaneous electrographic seizures and reduced power of gamma oscillations. Thus, Dlx5&6 appeared to be required for development and function of somal innervating (parvalbumin(+)) neocortical interneurons. This contrasts with Dlx1, whose function is required for dendrite innervating (calretinin(+), somatostatin(+), and neuropeptide Y(+)) interneurons (Cobos et al., 2005).
Wang
Yanling
Y
Department of Psychiatry, Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco, San Francisco, California 94158, USA. Yanling.wang@ucsf.edu
Dye
Catherine A
CA
Sohal
Vikaas
V
Long
Jason E
JE
Estrada
Rosanne C
RC
Roztocil
Tomas
T
Lufkin
Thomas
T
Deisseroth
Karl
K
Baraban
Scott C
SC
Rubenstein
John L R
JL
D000818:Animals; D001479:Basal Ganglia / Q000254:growth & development / Q000502:physiology / Q000503:physiopathology; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000254:growth & development* / Q000502:physiology* / Q000503:physiopathology; D003712:Dendrites / Q000473:pathology / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007395:Interneurons / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D060850:LIM-Homeodomain Proteins; D051258:MafB Transcription Factor / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology; D010320:Parvalbumins / Q000378:metabolism*; D010507:Periodicity; D019718:Receptors, CXCR4 / Q000378:metabolism; D012640:Seizures / Q000473:pathology / Q000503:physiopathology; D013687:Telencephalon / Q000254:growth & development / Q000502:physiology / Q000503:physiopathology; D014157:Transcription Factors
C514936:CXCR4 protein, mouse; C501120:Dlx5 protein, mouse; C100597:Dlx6 protein, mouse; D018398:Homeodomain Proteins; C498504:LHX6 protein, mouse; D060850:LIM-Homeodomain Proteins; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D019718:Receptors, CXCR4; D014157:Transcription Factors
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