Roberts C W, Sonder A M, Lumsden A, Korsmeyer S J
Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA.
Am J Pathol. 1995 May;146(5):1089-101.
Hox11 is the first member of a novel class of orphan homeobox genes. We report that Hox11 is expressed in a discrete temporal and spatially segmented pattern during embryonic development and appears critical for the specification of splenic cell fate. Expression is first observed in the developing muscle plates of branchial arches 1, 2, 3 and 4/6, and subsequently within motor neurons of cranial nerves V, VII, IX, and X, which innervate these muscles. Hox11 serves as a molecular maker distinguishing branchial from somatic motor nuclei. Additionally, Hox11 is expressed in the surface ectoderm of the first branchial arch in the region destined to become the tongue and teeth and then in ganglia innervating this area. However, Hox11-deficient mice have no apparent morphological of functional defects within these structures. Notably the closely related homeobox genes, Hox11L.1 and Hox1L1.2, were not expressed in a redundant pattern. Neither Hox11L1 nor Hox11L2 was expressed in the branchial arches or their motor nuclei within wild-type or Hox11-/- mice. Beginning at E11.5, Hox11 is normally expressed at a single site in the abdomen within splanchnic mesoderm destined to form the spleen, and Hox11-/- mice have no spleen. We noted no increase in cell death within the dorsal mesogastrium of Hox11-deficient mice. Instead the dorsal mesogastrium fails to separate from the stomach. Hox11-/- mice display a larger stomach and possibly pancreas, suggesting that these mesodermal cells now contribute to other organs.
Hox11是一类新型孤儿同源盒基因的首个成员。我们报告称,Hox11在胚胎发育过程中以离散的时间和空间分段模式表达,并且对于脾细胞命运的特化似乎至关重要。首先在第1、2、3和4/6鳃弓的发育中的肌板中观察到表达,随后在支配这些肌肉的第V、VII、IX和X颅神经的运动神经元中表达。Hox11作为区分鳃运动核与躯体运动核的分子标志物。此外,Hox11在第一鳃弓注定形成舌头和牙齿区域的表面外胚层中表达,然后在支配该区域的神经节中表达。然而,Hox11缺陷型小鼠在这些结构内没有明显的形态或功能缺陷。值得注意的是,密切相关的同源盒基因Hox11L.1和Hox1L1.2并非以冗余模式表达。在野生型或Hox11 - / - 小鼠中,Hox11L1和Hox11L2在鳃弓或其运动核中均未表达。从胚胎第11.5天开始,Hox11通常在腹部中一个注定形成脾脏的脏壁中胚层的单一部位表达,而Hox11 - / - 小鼠没有脾脏。我们注意到Hox11缺陷型小鼠的胃背系膜内细胞死亡没有增加。相反,胃背系膜未能与胃分离。Hox11 - / - 小鼠的胃和可能的胰腺更大,这表明这些中胚层细胞现在对其他器官有贡献。