2 969 707 entitled "Methods for Development and Use of Minimally Polarized Function Cell Micro-Aggregate Units in Tissue Applications Using LGR4
, LGR5, And LGR6 Expressing Epithelial Stem Cells." This patent relates to PolarityTE's unique micro-aggregate technology capable of assembling functional polarized tissue, as well as methods for producing compositions including these micro-aggregates, and the use of these micro-aggregates for therapeutic treatment of skin, skin repair and skin restoration.
This is in contrast with the effect of miR-34 in retinal cells, where this miRNA reduces cell proliferation by inhibiting LGR4 .
Tang et al., "LGR4 is a direct target of microRNA-34a and modulates the proliferation and migration of retinal pigment epithelial ARPE-19 cells," PLoS One, vol.
Loss of the leucine-rich repeat domain-containing G protein-coupled receptor 4 (Lgr4, also called Gpr48) has been implicated in anterior segment dysgenesis including iridocorneal attachment and elevated intraocular pressure leading to early onset retinal ganglion cell loss in mice that is similar to glaucomatous damage in humans 1].
Lgr4 has been shown to signal through classical [G.sub.[alpha]s]-mediated signaling in multiple systems.
The Lgr4 family members Lgr5 and 6 have been implicated in stem cell maintenance in a variety of tissues.
Lgr4 mRNA expression in mice was first detected at E7 and in adult mice was the highest in liver, then kidney, with moderate expression in muscle, heart, and brain, and low levels in testes and lung .
In one approach, a gene trap cassette was inserted in the first intron to generate a chimeric mRNA containing the N-terminal Leucine-rich repeat of Lgr4 fused to the CD4 transmembrane domain and the [beta]-galactosidase coding sequence [1, 20].
Lgr4 loss delays osteoblast differentiation, resulting in decreased embryonic bone formation; bone formation kinetics and bone mineral density were decreased through adulthood in [Lgr4.sup.-/-] mice .