Horng Sam, Kreiman Gabriel, Ellsworth Charlene, Page Damon, Blank Marissa, Millen Kathleen, Sur Mriganka
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
J Neurosci. 2009 Oct 28;29(43):13672-83. doi: 10.1523/JNEUROSCI.2127-09.2009.
Primary sensory nuclei of the thalamus process and relay parallel channels of sensory input into the cortex. The developmental processes by which these nuclei acquire distinct functional roles are not well understood. To identify novel groups of genes with a potential role in differentiating two adjacent sensory nuclei, we performed a microarray screen comparing perinatal gene expression in the principal auditory relay nucleus, the medial geniculate nucleus (MGN), and principal visual relay nucleus, the lateral geniculate nucleus (LGN). We discovered and confirmed groups of highly ranked, differentially expressed genes with qRT-PCR and in situ hybridization. A functional role for Zic4, a transcription factor highly enriched in the LGN, was investigated using Zic4-null mice, which were found to have changes in topographic patterning of retinogeniculate projections. Foxp2, a transcriptional repressor expressed strongly in the MGN, was found to be positively regulated by activity in the MGN. These findings identify roles for two differentially expressed genes, Zic4 and Foxp2, in visual and auditory pathway development. Finally, to test whether modality-specific patterns of gene expression are influenced by extrinsic patterns of input, we performed an additional microarray screen comparing the normal MGN to "rewired" MGN, in which normal auditory afferents are ablated and novel retinal inputs innervate the MGN. Data from this screen indicate that rewired MGN acquires some patterns of gene expression that are present in the developing LGN, including an upregulation of Zic4 expression, as well as novel patterns of expression which may represent unique processes of cross-modal plasticity.
丘脑的主要感觉核处理并将平行的感觉输入通道传递至皮层。这些核获得不同功能作用的发育过程尚未得到充分理解。为了鉴定在区分两个相邻感觉核中可能起作用的新基因群，我们进行了一项微阵列筛选，比较围产期基因在主要听觉中继核——内侧膝状体核（MGN）和主要视觉中继核——外侧膝状体核（LGN）中的表达。我们通过定量逆转录聚合酶链反应（qRT-PCR）和原位杂交发现并证实了高度排名、差异表达的基因群。使用Zic4基因敲除小鼠研究了在LGN中高度富集的转录因子Zic4的功能作用，发现这些小鼠在视网膜膝状体投射的拓扑模式上有变化。在MGN中强烈表达的转录抑制因子Foxp2被发现受MGN中活性的正向调节。这些发现确定了两个差异表达基因Zic4和Foxp2在视觉和听觉通路发育中的作用。最后，为了测试基因表达的模态特异性模式是否受外在输入模式的影响，我们进行了另一项微阵列筛选，比较正常的MGN和“重新布线”的MGN，在“重新布线”的MGN中，正常听觉传入纤维被切除，新的视网膜输入支配MGN。该筛选的数据表明，重新布线的MGN获得了一些在发育中的LGN中存在的基因表达模式，包括Zic4表达的上调，以及可能代表跨模态可塑性独特过程的新表达模式。
