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The Journal of Neuroscience, April 15, 2001, 21(8):2711-2725
Combinatorial Expression Patterns of LIM-Homeodomain and Other
Regulatory Genes Parcellate Developing Thalamus
Yasushi
Nakagawa and
Dennis D. M.
O'Leary
Molecular Neurobiology Laboratory, The Salk Institute, La Jolla,
California 92037
The anatomical and functional organization of dorsal thalamus (dTh)
and ventral thalamus (vTh), two major regions of the diencephalon, is
characterized by their parcellation into distinct cell groups, or
nuclei, that can be histologically defined in postnatal animals. However, because of the complexity of dTh and vTh and difficulties in
histologically defining nuclei at early developmental stages, our
understanding of the mechanisms that control the parcellation of dTh
and vTh and the differentiation of nuclei is limited. We have defined a
set of regulatory genes, which include five LIM-homeodomain transcription factors (Isl1, Lhx1,
Lhx2, Lhx5, and
Lhx9) and three other genes (Gbx2,
Ngn2, and Pax6), that are differentially
expressed in dTh and vTh of early postnatal mice in distinct but
overlapping patterns that mark nuclei or subsets of nuclei. These genes
exhibit differential expression patterns in dTh and vTh as early as
embryonic day 10.5, when neurogenesis begins; the expression of most of them is detected as progenitor cells exit the cell cycle. Soon thereafter, their expression patterns are very similar to those that we
observe postnatally, indicating that unique combinations of these genes
mark specific cell groups from the time they are generated to their
later differentiation into nuclei. Our findings suggest that these
genes act in a combinatorial manner to control the specification of
nuclei-specific properties of thalamic cells and the differentiation of
nuclei within dTh and vTh. These genes may also influence the
pathfinding and targeting of thalamocortical axons through both
cell-autonomous and non-autonomous mechanisms.
Key words:
dorsal thalamus; neuronal specification; thalamic nuclei; thalamocortical projection; transcription factors; LIM-homeodomain; Isl1; Lhx1; Lhx2; Lhx5; Lhx9; Pax6; Gbx2; Ngn2; RPTP ; ventral thalamus
Copyright © 2001 Society for Neuroscience 0270-6474/01/2182711-15$05.00/0
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