Zinc finger gene fez-like
functions in the formation of subplate neurons and thalamocortical axons
Hirata T, Suda Y, Nakao K, Narimatsu M, Hirano T and Hibi M
Dev Dyn 230(3):546-56 (2004)
SUMMARY
fez-like (fezl) is a forebrain-expressed zinc finger gene required for
the formation of the hypothalamic dopaminergic and serotonergic (monoaminergic)
neurons in zebrafish. To reveal its function in mammals, we analyzed the
expression of the mouse orthologue of fezl and generated fezl-deficient
mice by homologous recombination. Mouse fezl was expressed specifically
in the forebrain from embryonic day 8.5. At mid-gestation, fezl expression
was detected in subdomains of the forebrain, including the dorsal telencephalon
and ventral diencephalon. Unlike the zebrafish fezl mutant too few, the
fezl-deficient mice displayed normal development of hypothalamic monoaminergic
neurons, but showed abnormal "hyperactive" behavior. In fezl(-/-)
mice, the thalamocortical axons (TCA) were reduced in number and aberrantly
projected to the cortex. These mutants had a reduced number of subplate
neurons, which are involved in guiding the TCA from the dorsal thalamus,
although the subplate neurons were born normally. These results suggest
that fezl is required for differentiation or survival of the subplate
neurons, and reduction of the subplate neurons in fezl-deficient mice
leads to abnormal development of the TCA, providing a possible link between
the transcriptional regulation of forebrain development and hyperactive
behavior.
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