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ISDN2012_0201: Self powered biomems sensor for hydrocephalus shunts
Author(s) -
Rajendran Vinod
Publication year - 2012
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2012.10.025
Subject(s) - hydrocephalus , biomedical engineering , materials science , medicine , computer science , surgery
Solomon Snyder Dept. of Neuroscience, Johns Hopkins School of Medicine, United States E-mail address: jdemelo@jhmi.edu (J. de Melo). The LIM homeodomain transcription factor Lhx2 is an essential factor for the development of the mammalian retina. Lhx2 knockout mice are embryonic lethal and display complete anophthalmia with arrest of ocular development occurring at the optic vesicle stage. We demonstrate that Lhx2 is expressed in mitotically active retinal progenitors during embryonic development. Expression of Lhx2 becomes restricted to Müller glia (MG) and a subset of amacrine cells in the post-natal retina within which Lhx2 expression remains throughout adulthood. Utilizing a conditional Lhx2 knockout mouse we have demonstrated that loss of Lhx2 at approximately E10 results in mitotic arrest and microphthalmia. Deletion of Lhx2 in Muller glial precursors, however, resulted in a failure in MG formation resulting in laminar disruption and rosette formation in the outer nuclear layer (ONL). In vivo electroporation experiments were performed to generate retinas in which Lhx2 was deleted in a mosaic fashion. Electroporation of plasmids expressing Cre recombinase into floxed Lhx2 mice replicated the MG phenotype seen in the conditional knockout mice. Electroporation of the pro-glial bHLH transcription factor Hes5 promoted formation of MG; however, co-electroporation of Hes5 with cre into floxed Lhx2 mice blocked the enhanced MG formation. Furthermore, co-electroporation of Lhx2 with Hes5 into wild-type retinas also blocked the formation of MG. While loss of Lhx2 function resulted in failed MG development, electroporation of Lhx2 alone did not promote the formation of MG but instead resulted in the generation of wide-field amacrine cells. Intriguingly, generation of wide field amacrine cells was enhanced by co-electroporating Lhx2 with the bHLH transcription factor Neurog2. Taken together these results suggest a model where Lhx2 maintains the retinal progenitor state and is instructive for the generation of wide-field amacrine cells. However, upon commitment to a MG fate Lhx2 is absolutely required for the differentiation of MG.