Objective: 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.
Design: 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.
Results: 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.
Conclusions: 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.