Combinatorial expression patterns of LIM-homeodomain and other regulatory genes parcellate developing thalamus
Combinatorial expression patterns of LIM-homeodomain and other regulatory genes parcellate developing thalamus
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DOI：
10.1523/jneurosci.21-08-02711.2001
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发表时间：
2001-04-15
影响因子：
5.3
通讯作者：
O'Leary, DDM
中科院分区：
文献类型：
--
作者：
Nakagawa, Y;O'Leary, DDM
背侧丘脑（dTh）和腹侧丘脑（vTh），间脑的两个主要区域的解剖和功能组织，其特征在于它们被包裹成不同的细胞群，或核，可以在出生后的动物中被组织学定义。然而，由于dTh和vTh的复杂性和在早期发育阶段的细胞核的组织学定义的困难，我们对控制dTh和vTh的包裹和细胞核的分化的机制的理解是有限的。我们已经定义了一组调控基因，其中包括5个LIM同源结构域转录因子（Isl 1，Lhx 1，Lhx 2，Lhx 5和Lhx 9）和其他三个基因（Gbx 2，Ngn 2和Pau6），这些基因在出生后早期小鼠的dTh和vTh中以不同但重叠的模式差异表达，这些模式标志着细胞核或细胞核的子集。这些基因表现出差异表达模式dTh和vTh早在胚胎第10.5天，当神经发生开始，他们中的大多数的表达被检测到祖细胞退出细胞周期。此后不久，它们的表达模式与我们在出生后观察到的非常相似，这表明这些基因的独特组合标志着特定的细胞群，从它们产生到后来分化成细胞核。我们的研究结果表明，这些基因以组合的方式发挥作用，以控制丘脑细胞的核特异性特性的规范和dTh和vTh内的细胞核的分化。这些基因也可能通过细胞自主和非自主机制影响丘脑皮层轴突的寻路和靶向。
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 Pau6), 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.