Normal embryonic development and neonatal digit regeneration in mice overexpressing a stem cell factor, Sall4.
Normal embryonic development and neonatal digit regeneration in mice overexpressing a stem cell factor, Sall4.
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DOI：
10.1371/journal.pone.0267273
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
Kawakami, Yasuhiko
中科院分区：
文献类型：
--
作者：
Chen, Katherine Q.;Anderson, Aaron;Kawakami, Hiroko;Kim, Jennifer;Barrett, Janaya;Kawakami, Yasuhiko
Sall4编码一种转录因子，已知参与胚胎干细胞的多能性网络。已知Sall4在早期植入后小鼠胚胎中表达较高。在原肠胚形成后的早期阶段，Sall4在尾芽和远肢芽中高度表达，在那里祖细胞保持未分化状态。Sall4的表达在胚胎发育过程中迅速下调。我们之前通过在T （Brachyury）谱系中条件缺失Sall4证明了Sall4是肢体和后轴骨骼发育所必需的。为了深入了解Sall4在胚胎发育和出生后手指再生中的功能，我们通过tcree转基因和rosa26 - loxp -stop loxp -Sall4的新敲入等位基因在中胚层谱系中过表达Sall4。与以往研究中报道的Sall4功能丧失导致的严重缺陷相比，Sall4过表达导致胚胎和新生儿的形态和模式正常。sall4过表达小鼠的肢体长骨长度略有减少。在实验性截肢后，新生小鼠的指尖具有特定水平的再生能力。我们通过使用敏感的Sall4- lacz敲入报告基因表达来观察Sall4在指尖中的表达。Sall4过表达并未改变断肢后正常再生的末梢指骨的再生能力。此外，Sall4过表达并没有赋予截肢后通常不能再生的第二指骨再生能力。这些基因实验表明，Sall4的过表达不会改变尾骨和轴骨的发育，也不会改变新生儿手指的再生。结果表明，Sall4是一种纵容因素，而不是指导因素。
Sall4 encodes a transcription factor and is known to participate in the pluripotency network of embryonic stem cells. Sall4 expression is known to be high in early stage post-implantation mouse embryos. During early post-gastrulation stages, Sall4 is highly expressed in the tail bud and distal limb buds, where progenitor cells are maintained in an undifferentiated status. The expression of Sall4 is rapidly downregulated during embryonic development. We previously demonstrated that Sall4 is required for limb and posterior axial skeleton development by conditional deletion of Sall4 in the T (Brachyury) lineage. To gain insight into Sall4 functions in embryonic development and postnatal digit regeneration, we genetically overexpressed Sall4 in the mesodermal lineage by the TCre transgene and a novel knockin allele of Rosa26-loxP-stop-loxP-Sall4. In significant contrast to severe defects by Sall4 loss of function reported in previous studies, overexpression of Sall4 resulted in normal morphology and pattern in embryos and neonates. The length of limb long bones showed subtle reduction in Sall4-overexpression mice. It is known that the digit tip of neonatal mice has level-specific regenerative ability after experimental amputation. We observed Sall4 expression in the digit tip by using a sensitive Sall4-LacZ knock-in reporter expression. Sall4 overexpression did not alter the regenerative ability of the terminal phalange that normally regenerates after amputation. Moreover, Sall4 overexpression did not confer regenerative ability to the second phalange that normally does not regenerate after amputation. These genetic experiments show that overexpression of Sall4 does not alter the development of the appendicular and axial skeleton, or neonatal digit regeneration. The results suggest that Sall4 acts as a permissive factor rather than playing an instructive role.
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影响因子：
2.1
作者：
Muneoka, Ken;Allan, Christopher H.;Han, Manjong
通讯作者：
Han, Manjong
影响因子：
5.9
作者：
Chan AL;La HM;Legrand JMD;Mäkelä JA;Eichenlaub M;De Seram M;Ramialison M;Hobbs RM
通讯作者：
Hobbs RM
影响因子：
7.2
作者：
Erickson JR;Gearhart MD;Honson DD;Reid TA;Gardner MK;Moriarity BS;Echeverri K
通讯作者：
Echeverri K
影响因子：
9.8
作者：
Al-Baradie, R;Yamada, K;Engle, EC
通讯作者：
Engle, EC
影响因子：
3.3
作者：
Chen, Katherine Q.;Tahara, Naoyuki;Kawakami, Yasuhiko
通讯作者：
Kawakami, Yasuhiko