On the role of lateral stabilization during early patterning in the pancreas
On the role of lateral stabilization during early patterning in the pancreas
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DOI：
10.1098/rsif.2012.0766
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发表时间：
2013-02-06
影响因子：
3.9
通讯作者：
Brusch, Lutz
中科院分区：
文献类型：
--
作者：
de Back, Walter;Zhou, Joseph Xu;Brusch, Lutz
多能胰腺祖细胞在外分泌和内分泌谱系之间的细胞命运决定由Notch信号传导调节，由细胞-细胞相互作用介导。然而，Notch介导的侧抑制的经典模型不能解释内分泌细胞的分散的空间分布和细胞类型比在发育中的胰腺。基于体外腺泡-胰岛细胞转分化的证据，我们提出侧向稳定，即相邻祖细胞之间的正反馈，与侧向抑制平行作用，以调节胰腺中的模式形成。一个简单的数学模型的转录调控和细胞间的相互作用揭示了存在的多稳定性的空间模式，其同时发生的原因散射的内分泌细胞中存在的噪音。散射模式允许通过调节横向稳定强度来控制内分泌与外分泌细胞类型比。这些理论结果表明，在器官发育的谱系规范，空间格局和细胞类型的比例控制的横向稳定以前未被认识到的作用。
The cell fate decision of multi-potent pancreatic progenitor cells between the exocrine and endocrine lineages is regulated by Notch signalling, mediated by cell-cell interactions. However, canonical models of Notch-mediated lateral inhibition cannot explain the scattered spatial distribution of endocrine cells and the cell-type ratio in the developing pancreas. Based on evidence from acinar-to-islet cell transdifferentiation in vitro, we propose that lateral stabilization, i.e. positive feedback between adjacent progenitor cells, acts in parallel with lateral inhibition to regulate pattern formation in the pancreas. A simple mathematical model of transcriptional regulation and cell-cell interaction reveals the existence of multi-stability of spatial patterns whose simultaneous occurrence causes scattering of endocrine cells in the presence of noise. The scattering pattern allows for control of the endocrine-to-exocrine cell-type ratio by modulation of lateral stabilization strength. These theoretical results suggest a previously unrecognized role for lateral stabilization in lineage specification, spatial patterning and cell-type ratio control in organ development.