Enpp2/Autotaxin in dermal papilla precursors is dispensable for hair follicle morphogenesis.

Enpp2/Autotaxin in dermal papilla precursors is dispensable for hair follicle morphogenesis.
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DOI:
10.1038/jid.2013.140
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发表时间:
2013-10
影响因子:
6.5
通讯作者:
Rendl, Michael
Rendl, Michael
中科院分区:
医学1区
文献类型:
--
作者:
Grisanti, Laura;Rezza, Amelie;Clavel, Carlos;Sennett, Rachel;Rendl, Michael

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系统消融以前确定的毛乳头(DP)的签名基因在胚胎DP前体揭示其功能的作用,在毛囊形态发生。在这项研究中,我们验证Enpp 2/Autotaxin作为一个最高表达的签名基因在出生后DP,并证明这种溶血磷脂酸(LPA)产生的酶在胚胎真皮冷凝物的特异性表达。我们进一步确定真皮和表皮的几个LPA受体的表达,表明LPA信号可能有助于卵泡形态发生间充质和上皮隔室。然后,我们利用最近表征的表达Cre的Tbx 18敲入系有条件地消融胚胎DP前体中的Enpp 2。尽管在E14.5真皮冷凝物中进行了有效的基因敲除,但形态发生规律地进行,所有毛囊类型的数量、长度和大小都正常,这表明Enpp 2不是毛囊形成所必需的。为了询问DP标签基因表达,我们最终分离对照和Enpp 2无效DP前体,并鉴定LIPH(一种替代的LPA产生酶)的表达和上调,表明该基因可以在功能上补偿Enpp 2的缺失。我们的结论是,未来共同消融两个LPA生产酶或几个LPA受体可能揭示LPA信号在毛囊形态发生的功能作用。
Systematic ablation of previously identified dermal papilla (DP) signature genes in embryonic DP precursors will reveal their functional roles during hair follicle morphogenesis. In this study we validate Enpp2/Autotaxin as one of the highest expressed signature genes in postnatal DP, and demonstrate specific expression of this lysophosphatidic acid (LPA) generating enzyme in embryonic dermal condensates. We further identify dermal and epidermal expression of several LPA receptors suggesting that LPA signaling could contribute to follicle morphogenesis in both mesenchymal and epithelial compartments. We then utilize the recently characterized Cre-expressing Tbx18 knock-in line to conditionally ablate Enpp2 in embryonic DP precursors. Despite efficient gene knockout in E14.5 dermal condensates, morphogenesis proceeds regularly with normal numbers, lengths and sizes of all hair follicle types, suggesting that Enpp2 is not required for hair follicle formation. To interrogate DP signature gene expression, we finally isolate control and Enpp2 null DP precursors and identify the expression and upregulation of LIPH, an alternative LPA producing enzyme, suggesting that this gene could functionally compensate for the absence of Enpp2. We conclude that future co-ablation of both LPA producing enzymes or of several LPA receptors may reveal the functional role of LPA signaling during hair follicle morphogenesis.
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