Combined in silico and in vivo analyses reveal role of Hes1 in taste cell differentiation.
Combined in silico and in vivo analyses reveal role of Hes1 in taste cell differentiation.
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DOI：
10.1371/journal.pgen.1000443
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发表时间：
2009-04
期刊：
影响因子：
4.5
通讯作者：
Kondo T
中科院分区：
文献类型：
--
作者：
Ota MS;Kaneko Y;Kondo K;Ogishima S;Tanaka H;Eto K;Kondo T
味觉对动物的生存至关重要。虽然味觉信号转导机制的研究已经提供了关于味觉受体钙信号分子（trcsm，甜/苦/鲜味味觉信号转导所必需的）的详细信息，但味觉细胞的个体发生仍在很大程度上是未知的。我们采用了一种新颖的方法，通过硅和体内分析相结合来研究小鼠味觉系统发育的分子调控。在发现TRCSM共定位于发育中的环valvalate乳头（CVP）后，我们使用TRCSM上游调控区域的计算分析来研究TRCSM转录共同调控网络的可能性。基于这一分析，我们确定Hes1可能是一个共同的调节因子，并研究了其在体内的功能。表达谱分析显示，核HES1的表达降低与II型味觉细胞标志物的表达相关。E18期后，Hes1−/−突变体的CVP比其野生型幼崽的CVP多出5倍以上的trcsm免疫反应细胞。因此，根据我们的综合分析，Hes1可能在味蕾发育过程中协调味觉细胞分化中发挥作用。味觉由五种基本形态组成：甜、苦、鲜、酸、咸。特殊的味觉细胞感知食物中的各种化学信号。大约100个味觉细胞聚集成洋葱状的簇状物，称为味蕾，它们位于舌上皮和口腔粘膜的味觉乳头上。在五种味觉模式中，负责甜味、苦味和鲜味的味觉刺激物由一组G蛋白偶联的味觉受体识别，并且受体刺激后利用的信号转导途径具有共同的分子。然而，在味觉细胞发育过程中，这些分子是如何被调节的，这在很大程度上仍然是未知的。基于先前已知的味觉感知系统信号转导通路信息，我们进行了计算机分析，以识别味觉干细胞/ II型味觉细胞的祖细胞（负责甜味、苦味和鲜味味觉）。我们发现了几种可能结合味觉相关钙信号分子（trcsm）调控区域的转录因子，并确定了Hes1作为trcsm共同调控因子的潜在候选者。对野生型和Hes1突变小鼠的体内分析证实，Hes1调节苦味、甜味和鲜味感知细胞的分化。
The sense of taste is of critical importance to animal survival. Although studies of taste signal transduction mechanisms have provided detailed information regarding taste receptor calcium signaling molecules (TRCSMs, required for sweet/bitter/umami taste signal transduction), the ontogeny of taste cells is still largely unknown. We used a novel approach to investigate the molecular regulation of taste system development in mice by combining in silico and in vivo analyses. After discovering that TRCSMs colocalized within developing circumvallate papillae (CVP), we used computational analysis of the upstream regulatory regions of TRCSMs to investigate the possibility of a common regulatory network for TRCSM transcription. Based on this analysis, we identified Hes1 as a likely common regulatory factor, and examined its function in vivo. Expression profile analyses revealed that decreased expression of nuclear HES1 correlated with expression of type II taste cell markers. After stage E18, the CVP of Hes1−/ − mutants displayed over 5-fold more TRCSM-immunoreactive cells than did the CVP of their wild-type littermates. Thus, according to our composite analyses, Hes1 is likely to play a role in orchestrating taste cell differentiation in developing taste buds. The sensation of taste is composed of five basic modalities: sweet, bitter, umami, sour, and salty. Specialized taste cells perceive the various chemical cues within food. About 100 taste cells assemble into onion-shaped clusters called taste buds, which are located on taste papillae in the tongue epithelium and on oral mucosa. Of the five taste modalities, the taste stimulants responsible for sweet, bitter, and umami tastes are recognized by a group of G protein–coupled taste receptors, and the signal transduction pathways utilized following receptor stimulation share common molecules. However, it is still largely unknown how these molecules are regulated during taste cell development. We performed computer analyses based on previously known information about signal transduction pathways involved in the taste-sensing system to identify taste stem cells/progenitor factors of type II taste cells (responsible for sweet, bitter, and umami taste sensations). We found several transcription factors likely to bind to the regulatory regions of taste-related calcium signaling molecules (TRCSMs), and identified Hes1 as a potential candidate for common regulatory factors of TRCSMs. In vivo analyses using wild-type and Hes1 mutant mice confirmed that Hes1 regulates differentiation of bitter-, sweet-, and umami-sensing cells.
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影响因子：
3.5
作者：
Asano-Miyoshi, M;Abe, K;Emori, Y
通讯作者：
Emori, Y
DOI：
10.1083/jcb.200509084
发表时间：
2006-05-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Moriyama M;Osawa M;Mak SS;Ohtsuka T;Yamamoto N;Han H;Delmas V;Kageyama R;Beermann F;Larue L;Nishikawa S
通讯作者：
Nishikawa S
影响因子：
1.5
作者：
Mishra, Rakesh K.;Yamagishi, Takumi;Kondo, Takashi
通讯作者：
Kondo, Takashi
影响因子：
5.3
作者：
DeFazio, RA;Dvoryanchikov, G;Chaudhari, N
通讯作者：
Chaudhari, N
影响因子：
4.6
作者：
Hatakeyama, J;Bessho, Y;Kageyama, R
通讯作者：
Kageyama, R