Centre for Organismal Studies (COS), University of Heidelberg, Im Neuenheimer Feld 329, 69120 Heidelberg, Germany.
Development. 2014 Feb;141(3):639-49. doi: 10.1242/dev.098731.
Hox genes are classically ascribed to function in patterning the anterior-posterior axis of bilaterian animals; however, their role in directing molecular mechanisms underlying morphogenesis at the cellular level remains largely unstudied. We unveil a non-classical role for the zebrafish hoxb1b gene, which shares ancestral functions with mammalian Hoxa1, in controlling progenitor cell shape and oriented cell division during zebrafish anterior hindbrain neural tube morphogenesis. This is likely distinct from its role in cell fate acquisition and segment boundary formation. We show that, without affecting major components of apico-basal or planar cell polarity, Hoxb1b regulates mitotic spindle rotation during the oriented neural keel symmetric mitoses that are required for normal neural tube lumen formation in the zebrafish. This function correlates with a non-cell-autonomous requirement for Hoxb1b in regulating microtubule plus-end dynamics in progenitor cells in interphase. We propose that Hox genes can influence global tissue morphogenesis by control of microtubule dynamics in individual cells in vivo.
Hox 基因通常被认为在调控两侧对称动物的前后轴模式形成中发挥作用;然而,它们在指导细胞水平的形态发生的分子机制中的作用在很大程度上仍未得到研究。我们揭示了斑马鱼 hoxb1b 基因的非经典作用,该基因与哺乳动物 Hoxa1 具有祖先功能,在控制斑马鱼前后脑神经管形态发生中的祖细胞形状和定向细胞分裂中发挥作用。这可能与它在细胞命运获得和节段边界形成中的作用不同。我们表明,Hoxb1b 不影响顶底或平面细胞极性的主要成分,而是在定向神经龙骨对称有丝分裂期间调节有丝分裂纺锤体旋转,这对于正常的斑马鱼神经管管腔形成是必需的。该功能与 Hoxb1b 在调节有丝分裂期间祖细胞中微管正极动力学的非细胞自主需求相关。我们提出,Hox 基因可以通过控制体内单个细胞中的微管动力学来影响整体组织形态发生。