Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
J Mol Neurosci. 2012 Feb;46(2):293-302. doi: 10.1007/s12031-011-9563-x. Epub 2011 Jun 24.
Sall3 is a member of a gene family with homology to the spalt gene of Drosophila melanogaster, encoding transcription factors, and acts as downstream target of hedgehog. Vertebrate homologues of spalt have been shown to be involved in development of the limbs and nervous system and several organs including the kidney and heart; mutations in the genes are implicated in several human genetic disorders. Recent studies have shown a total loss of olfactory bulb (OB) dopaminergic (DA) neurons in Sall3-null mice. We assume that tyrosine hydroxylase (TH) may be regulated by Sall3 in OB. In this study, we find that Sall3 and TH co-localize in glomerular layer (GL) of OB. Furthermore, we demonstrate a significant induction of the proximal TH promoter transcription activity by Sall3 in dual-luciferase reporter assay and a reduction of TH expression level in Sall3-deficient cell lines. Collectively, these findings support the notion that Sall3 correlates with the expression of TH in mouse OB and may have a role in OB DA neuron development by regulating TH gene expression. The results from this study may advance our understanding of the molecular pathways of OB in the DA neuron development and differentiation.
Sall3 是果蝇 spalt 基因同源基因家族的成员,编码转录因子,作为 hedgehog 的下游靶标。脊椎动物 spalt 的同源物已被证明参与四肢和神经系统以及包括肾脏和心脏在内的几个器官的发育;这些基因的突变与几种人类遗传疾病有关。最近的研究表明,Sall3 缺失的小鼠嗅球(OB)多巴胺能(DA)神经元完全缺失。我们假设酪氨酸羟化酶(TH)可能受 OB 中的 Sall3 调节。在这项研究中,我们发现 Sall3 和 TH 在 OB 的肾小球层(GL)中共定位。此外,我们在双荧光素酶报告基因检测中证明 Sall3 显著诱导近端 TH 启动子转录活性,并且在 Sall3 缺失的细胞系中 TH 表达水平降低。总之,这些发现支持 Sall3 与小鼠 OB 中 TH 的表达相关的观点,并且可能通过调节 TH 基因表达在 OB DA 神经元发育中发挥作用。这项研究的结果可能有助于我们理解 OB 在 DA 神经元发育和分化中的分子途径。