Apicobasal polarity is known to affect epithelial morphogenesis and cell differentiation, but it remains unknown how these processes are mechanistically orchestrated. We find that ligand-specific EGFR signalling via PI(3)K and Rac1 autonomously modulates apicobasal polarity to enforce the sequential control of morphogenesis and cell differentiation. Initially, EGF controls pancreatic tubulogenesis by negatively regulating apical polarity induction. Subsequently, betacellulin, working via inhibition of atypical protein kinase C (aPKC), causes apical domain constriction within neurogenin3⁺ endocrine progenitors, which results in reduced Notch signalling, increased neurogenin3 expression, and β-cell differentiation. Notably, the ligand-specific EGFR output is not driven at the ligand level, but seems to have evolved in response to stage-specific epithelial influences. The EGFR-mediated control of β-cell differentiation via apical polarity is also conserved in human neurogenin3⁺ cells. We provide insight into how ligand-specific EGFR signalling coordinates epithelial morphogenesis and cell differentiation via apical polarity dynamics.

中文翻译：

---

EGFR信号传导通过调节apapobasal极性控制细胞命运和胰腺器官发生。

已知顶端基极性会影响上皮形态发生和细胞分化，但是如何机械地协调这些过程仍是未知的。我们发现通过PI（3）K和Rac1的配体特异性EGFR信号传导自主调节突触基底极性，以强制顺序控制形态发生和细胞分化。最初，EGF通过负向调节心尖极性诱导来控制胰腺微管发生。随后，β纤维素通过抑制非典型蛋白激酶C（aPKC）起作用，导致神经生成素3 ^+中的根尖结构域收缩内分泌祖细胞，导致Notch信号减少，neurogenin3表达增加和β细胞分化。值得注意的是，配体特异的EGFR输出不是在配体水平上驱动的，而是响应于阶段特异性上皮的影响而进化的。在人Neurogenin3 ⁺细胞中，EGFR介导的通过顶极对β细胞分化的控制也被保守。我们提供洞察配体特异性EGFR信号如何通过顶极动力学来协调上皮形态发生和细胞分化。