Notch regulation of progenitor cell behavior in quiescent and regenerating auditory epithelium of mature birds.
Notch regulation of progenitor cell behavior in quiescent and regenerating auditory epithelium of mature birds.
复制标题
DOI：
10.1016/j.ydbio.2008.10.033
复制
发表时间：
2009-02-01
影响因子：
2.7
通讯作者：
Stone, Jennifer
中科院分区：
文献类型：
--
作者：
Daudet, Nicolas;Gibson, Robin;Shang, Jialin;Bernard, Amy;Lewis, Julian;Stone, Jennifer
与哺乳动物不同，鸟类在受伤后再生听觉毛细胞（HC）。在再生过程中，成熟的非感觉支持细胞（SC）通过非有丝分裂或有丝分裂机制离开静止状态并转化为HC。在胚胎发生期间，来自新生HC的Notch配体施加侧向抑制，限制HC产生。在这里，我们研究了Notch信号传导是否需要（1）在成熟的鸟类中维持未受损的听觉上皮中的HC/SC模式或（2）一旦HC受损就控制SC行为。我们发现Notch途径基因在成熟的未受损上皮中转录，HC损伤后，其转录在有丝分裂活性最高的区域上调。在体外治疗与DAPT，抑制剂的Notch活性，没有影响SC在未受损的上皮。HC损伤后，DAPT对SC分裂无直接影响。然而，在损伤后，DAPT通过有丝分裂和非有丝分裂机制以SC为代价引起HC过度再生。相反，损伤后SC中活化Notch的过表达使它们保持其表型并抑制HC再生。因此，通过Notch的信号传导不是健康上皮中SC静止或损伤后启动HC再生所需的。相反，Notch可以防止SC在损伤后再生过多的HC。
Unlike mammals, birds regenerate auditory hair cells (HCs) after injury. During regeneration, mature non-sensory supporting cells (SCs) leave quiescence and convert into HCs, through non-mitotic or mitotic mechanisms. During embryogenesis, Notch ligands from nascent HCs exert lateral inhibition, restricting HC production. Here, we examined whether Notch signalling (1) is needed in mature birds to maintain the HC/SC pattern in the undamaged auditory epithelium or (2) governs SC behavior once HCs are injured. We show that Notch pathway genes are transcribed in the mature undamaged epithelium, and after HC injury, their transcription is upregulated in the region of highest mitotic activity. In vitro treatment with DAPT, an inhibitor of Notch activity, had no effect on SCs in the undamaged epithelium. Following HC damage, DAPT had no direct effect on SC division. However, after damage, DAPT caused excessive regeneration of HCs at the expense of SCs, through both mitotic and non-mitotic mechanisms. Conversely, overexpression of activated Notch in SCs after damage caused them to maintain their phenotype and inhibited HC regeneration. Therefore, signalling through Notch is not required for SC quiescence in the healthy epithelium or to initiate HC regeneration after damage. Rather, Notch prevents SCs from regenerating excessive HCs after damage.
登录
查看更多内容
影响因子：
2.7
作者：
GINZBERG, RD;GILULA, NB
通讯作者：
GILULA, NB
DOI：
10.1083/jcb.137.6.1287
发表时间：
1997-06-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hasson T;Gillespie PG;Garcia JA;MacDonald RB;Zhao Y;Yee AG;Mooseker MS;Corey DP
通讯作者：
Corey DP
影响因子：
2.5
作者：
Cafaro, Jon;Lee, Gi Soo;Stone, Jennifer S.
通讯作者：
Stone, Jennifer S.
影响因子：
2.8
作者：
Goodyear, R;Killick, R;Richardson, GP
通讯作者：
Richardson, GP
影响因子：
4.5
作者：
Kiernan AE;Xu J;Gridley T
通讯作者：
Gridley T