Melnick Michael, Petryk Anna, Abichaker George, Witcher Dan, Person Anthony D, Jaskoll Tina
Laboratory for Developmental Genetics, University of Southern California, 925 W 34th Street, DEN 4266, Los Angeles, CA 90089-0641, USA.
Arch Oral Biol. 2006 May;51(5):433-8. doi: 10.1016/j.archoralbio.2005.09.010. Epub 2005 Nov 14.
Mouse Twisted gastrulation gene (Twsg1) expression is found throughout embryonic development, including substantial levels in the first branchial arch that gives rise to the submandibular salivary gland (SMG). We addressed the proposition that normal Twsg1 expression is critical to normal SMG ontogenesis.
Utilizing C57BL/6 embryos that were Twsg1-/- homozygotes, as well as wild type and heterozygote littermates, we investigated SMG development from gestational day 13 to newborn.
Twsg1 protein is immunodetected in epithelia throughout SMG development. Twsg1-/- embryos display widely variable craniofacial phenotypes that range from normal to severe holoprosencephaly/agnathia with no mandibular arch or stomodeum. The SMG phenotypes are correlated with the external craniofacial phenotype, ranging from normal to agenesis/aplasia.
It is evident that normal Twsg1 expression is critical for normal mouse SMG ontogenesis. Twsg1 loss of function is ultimately epistatic to the epigenome under normal physiologic conditions, but not always so. The reduced penetrance and variable expressivity seen in the SMGs of Twsg1-/- embryos is a challenging enigma.
小鼠扭曲原肠胚形成基因（Twsg1）的表达在整个胚胎发育过程中均有发现，包括在形成下颌下唾液腺（SMG）的第一鳃弓中有大量表达。我们探讨了正常Twsg1表达对正常SMG个体发生至关重要这一命题。
利用Twsg1基因纯合缺失的C57BL/6胚胎以及野生型和杂合子同窝仔，我们研究了从妊娠第13天到新生期的SMG发育情况。
在整个SMG发育过程中，Twsg1蛋白在上皮细胞中可通过免疫检测到。Twsg1基因纯合缺失的胚胎表现出广泛多样的颅面表型，从正常到严重的前脑无裂畸形/无颌畸形，无下颌弓或口凹。SMG表型与外部颅面表型相关，从正常到发育不全/发育不良。
显然，正常Twsg1表达对正常小鼠SMG个体发生至关重要。在正常生理条件下，Twsg1功能丧失最终对表观基因组具有上位性，但并非总是如此。在Twsg1基因纯合缺失胚胎的SMG中观察到的较低外显率和可变表达率是一个具有挑战性的谜团。
