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Hox gene activity directs physical forces to differentially shape chick small and large intestinal epithelia
Developmental Cell ( IF 10.7 ) Pub Date : 2024-08-07 , DOI: 10.1016/j.devcel.2024.07.012 Hasreet K Gill 1 , Sifan Yin 2 , Nandan L Nerurkar 3 , John C Lawlor 1 , ChangHee Lee 1 , Tyler R Huycke 4 , L Mahadevan 5 , Clifford J Tabin 1
Developmental Cell ( IF 10.7 ) Pub Date : 2024-08-07 , DOI: 10.1016/j.devcel.2024.07.012 Hasreet K Gill 1 , Sifan Yin 2 , Nandan L Nerurkar 3 , John C Lawlor 1 , ChangHee Lee 1 , Tyler R Huycke 4 , L Mahadevan 5 , Clifford J Tabin 1
Affiliation
Hox transcription factors play crucial roles in organizing developmental patterning across metazoa, but how these factors trigger regional morphogenesis has largely remained a mystery. In the developing gut, Hox genes help demarcate identities of intestinal subregions early in embryogenesis, which ultimately leads to their specialization in both form and function. Although the midgut forms villi, the hindgut develops sulci that resolve into heterogeneous outgrowths. Combining mechanical measurements of the embryonic chick intestine and mathematical modeling, we demonstrate that the posterior Hox gene HOXD13 regulates biophysical phenomena that shape the hindgut lumen. We further show that HOXD13 acts through the transforming growth factor β (TGF-β) pathway to thicken, stiffen, and promote isotropic growth of the subepithelial mesenchyme—together, these features lead to hindgut-specific surface buckling. TGF-β, in turn, promotes collagen deposition to affect mesenchymal geometry and growth. We thus identify a cascade of events downstream of positional identity that direct posterior intestinal morphogenesis.
中文翻译:
Hox 基因活性引导物理力对雏鸡的小肠上皮细胞和大肠上皮细胞形成差异
Hox 转录因子在组织跨后生动物的发育模式中起着至关重要的作用,但这些因素如何触发区域形态发生在很大程度上仍然是一个谜。在发育中的肠道中,Hox 基因有助于在胚胎发生早期划分肠道亚区的身份,这最终导致它们在形式和功能上的专业化。虽然中肠形成绒毛,但后肠发育出沟,分解成异质性生长物。结合胚胎雏鸡肠道的机械测量和数学建模,我们证明后 Hox 基因 HOXD13 调节塑造后肠腔的生物物理现象。我们进一步表明,HOXD13 通过转化生长因子 β (TGF-β) 途径发挥作用,使上皮下间充质增厚、变硬并促进各向同性生长——这些特征共同导致后肠特异性表面屈曲。反过来,TGF-β 促进胶原蛋白沉积,从而影响间充质几何形状和生长。因此,我们确定了指导后肠形态发生的位置身份下游的一连串事件。
更新日期:2024-08-07
中文翻译:
Hox 基因活性引导物理力对雏鸡的小肠上皮细胞和大肠上皮细胞形成差异
Hox 转录因子在组织跨后生动物的发育模式中起着至关重要的作用,但这些因素如何触发区域形态发生在很大程度上仍然是一个谜。在发育中的肠道中,Hox 基因有助于在胚胎发生早期划分肠道亚区的身份,这最终导致它们在形式和功能上的专业化。虽然中肠形成绒毛,但后肠发育出沟,分解成异质性生长物。结合胚胎雏鸡肠道的机械测量和数学建模,我们证明后 Hox 基因 HOXD13 调节塑造后肠腔的生物物理现象。我们进一步表明,HOXD13 通过转化生长因子 β (TGF-β) 途径发挥作用,使上皮下间充质增厚、变硬并促进各向同性生长——这些特征共同导致后肠特异性表面屈曲。反过来,TGF-β 促进胶原蛋白沉积,从而影响间充质几何形状和生长。因此,我们确定了指导后肠形态发生的位置身份下游的一连串事件。