PURPOSE: Smad4, a key intracellular mediator in TGF-β signaling, plays a critical role in the normal development of many tissues/organs. However, its functional role in the development of the lacrimal gland (LG) has never been reported. The aim of this study was to investigate the role Smad4 may play in the development of LG by using Smad4 conditional knockout mice and comparing their LG changes with the LG in normal control mice. METHODS: Smad4 in the LG, as well as in the lens, cornea, and ectoderm of the eyelids, was conditionally inactivated by using Pax6 promoter-driven Cre-transgenic mice. Lac Z reporter was used to visualize the developing LG by X-gal staining, and standard histologic approaches were used to reveal morphologic alterations. RESULTS: Inactivation of Smad4 resulted in reduction in the size and number of acini in the embryonic LG and in pigment accumulation within the LG, although it did not affect the formation of the primary lacrimal bud. After birth, the LG from Smad4-mutant mice developed slowly, and pigment was observed starting from the P7 mutant LG. Thereafter, the mutant LG was considerably smaller than the normal LG and was eventually replaced by adipose tissue. CONCLUSIONS: These results support the notion that Smad4 is essential for the normal development and maintenance of the mouse LG.
PURPOSE:Smad4, a key intracellular mediator in TGF-β signaling, plays a critical role in the normal development of many tissues/organs. However, its functional role in the development of the lacrimal gland (LG) has never been reported. The aim of this study was to investigate the role Smad4 may play in the development of LG by using Smad4 conditional knockout mice and comparing their LG changes with the LG in normal control mice. METHODS:Smad4 in the LG, as well as in the lens, cornea, and ectoderm of the eyelids, was conditionally inactivated by using Pax6 promoter-driven Cre-transgenic mice. Lac Z reporter was used to visualize the developing LG by X-gal staining, and standard histologic approaches were used to reveal morphologic alterations. RESULTS: Inactivation of Smad4 resulted in reduction in the size and number of acini in the embryonic LG and in pigment accumulation within the LG, although it did not affect the formation of the primary lacrimal bud. After birth, the LG from Smad4-mutant mice developed slowly, and pigment was observed starting from the P7 mutant LG. Thereafter, the mutant LG was considerably smaller than the normal LG and was eventually replaced by adipose tissue. CONCLUSIONS: These results support the notion that Smad4 is essential for the normal development and maintenance of the mouse LG.
Authors: Yi Pan; Christian Carbe; Andrea Powers; Eric E Zhang; Jeffrey D Esko; Kay Grobe; Gen-Sheng Feng; Xin Zhang Journal: Development Date: 2007-12-12 Impact factor: 6.868
Authors: Takeshi Umazume; William M Thomas; Sabrina Campbell; Hema Aluri; Suharika Thotakura; Driss Zoukhri; Helen P Makarenkova Journal: Invest Ophthalmol Vis Sci Date: 2015-12 Impact factor: 4.799
Authors: Richard N Wang; Jordan Green; Zhongliang Wang; Youlin Deng; Min Qiao; Michael Peabody; Qian Zhang; Jixing Ye; Zhengjian Yan; Sahitya Denduluri; Olumuyiwa Idowu; Melissa Li; Christine Shen; Alan Hu; Rex C Haydon; Richard Kang; James Mok; Michael J Lee; Hue L Luu; Lewis L Shi Journal: Genes Dis Date: 2014-09
Authors: D'Juan T Farmer; Jennifer K Finley; Feeling Y Chen; Estefania Tarifeño-Saldivia; Nancy A McNamara; Sarah M Knox; Michael T McManus Journal: Dev Biol Date: 2017-05-13 Impact factor: 3.148