Journal
DEVELOPMENTAL NEUROBIOLOGY
Volume 68, Issue 7, Pages 917-925Publisher
WILEY
DOI: 10.1002/dneu.20626
Keywords
cerebral cortex; Cux-1; Cux-2; interneurons
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Funding
- Howard Hughes Medical Institute Funding Source: Medline
- NCRR NIH HHS [M01 RR001032-290837, M01 RR001032] Funding Source: Medline
- NINDS NIH HHS [R01 NS035129, R01 NS035129-14] Funding Source: Medline
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Homeodomain transcription factors play important roles in the specification and differentiation of neuronal subpopulations. In the cerebral cortex, the expression patterns of Cux-1 and Cux-2 in the medial ganglionic eminence (MGE) suggest a role for these transcription factors in the development of interneurons, a heterogeneous neuronal population. In this report, we describe expression of Cux-1 and Cux-2 proteins in Reelin-secreting interneurons of the cortical plate, but not in calretinin or parvalbumin subpopulations. The role of Cux genes in the development of Reelin positive neurons was studied using Cux-1 and Cux-2 knockout mice. These experiments demonstrate that Cux-1-/-; Cux-2-/- double mutation is embryonically lethal. Although this phenotype is highly penetrant, a small proportion of mice develop to birth (PO). Analysis of these animals demonstrate that expression of Reelin is completely absent in layers II-IV of Cux-1-/-; Cux-2-/- double mutant mice, but it is not affected in the cortex of Cux-1-/- or Cux-2-/- single mutants. No Cux-1-/-; Cux-2-/- double-mutant were collected after PO. Since, GABA-ergic populations mature at late postnatal stages, this did not allow us to analyze the expression of subclass specific markers and define the affected interneuron subpopulations. Our analysis of Cux-1-/-; Cux-2-/- double mutant thus demonstrates essential yet redundant roles for Cux-1 and Cux-2 in specifying Reelin expressing cortical interneurons. (C) 2008 Wiley Periodicals, Inc.
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