Severe Defects in Proliferation and Differentiation of Lens Cells in Foxe3 Null Mice

Abstract

During mouse eye development, the correct formation of the lens occurs as a result of reciprocal interactions between the neuroectoderm that forms the retina and surface ectoderm that forms the lens. Although many transcription factors required for early lens development have been identified, the mechanism and genetic interactions mediated by them remain poorly understood. Foxe3 encodes a winged helix-forkhead transcription factor that is initially expressed in the developing brain and in the lens placode and later restricted exclusively to the anterior lens epithelium. Here, we show that targeted disruption of Foxe3 results in abnormal development of the eye. Cells of the anterior lens epithelium show a decreased rate of proliferation, resulting in a smaller than normal lens. The anterior lens epithelium does not properly separate from the cornea and frequently forms an unusual, multilayered tissue. Because of the abnormal differentiation, lens fiber cells do not form properly, and the morphogenesis of the lens is greatly affected. The abnormally differentiated lens cells remain irregular in shape, and the lens becomes vacuolated. The defects in lens development correlate with changes in the expression of growth and differentiation factor genes, including DNase II-like acid DNase, Prox1, p57, and PDGF␣ receptor. As a result of abnormal lens development, the cornea and the retina are also affected. While Foxe3 is also expressed in a distinct region of the embryonic brain, we have not observed abnormal development of the brain in Foxe3 ؊/؊ animals.

The New Era of the Lymphatic System: No Longer Secondary to the Blood Vascular System

“…In colon cancer cells ) and hippocampus cells (Karalay et al 2011), Prox1 is regulated by the Wnt signal through two binding sites of b-catenin/TCF found in the Prox1 enhancer region at 249 kb and 243 kb upstream of the Prox1 start codon, which induce colon cancer progression and neuronal cell differentiation, respectively. Mash1 (Torii et al 1999) and Foxe3 (Medina-Martinez et al 2005) were found to regulate Prox1 expression in the nervous system and lens, respectively.…”

Eye-specific expression of an ancestral jellyfish PaxB gene interferes with Pax6 function despite its conserved Pax6/Pax2 characteristics

“…First, the present findings that the genes acting downstream of Pax6 during lens development encoding Mab2111, FoxE3, Prox1 and crystallins are reduced, while expression of Six3, Meis1 and Meis2, all genes upstream of Pax6, are unaffected in the lenses of the PaxB transgenic mice. Second, targeted disruption of FoxE3, whose expression critically depends on Pax6 (Blixt et al, 2007) results in lens defects resembling the phenotype of PaxB transgenic mice (Blixt et al, 2000;Medina-Martinez et al, 2005). Moreover delayed lens development in PaxB transgenic mice resembled the smaller lens pit or vesicle of Pax6 Sey/+ heterozygote and Pax6 ∆EE/ ∆EE mice (van Raamsdonk and Tilghman, 2000;Dimanlig et al, 2001).…”

“…The lens defects in PaxB transgenic mice prompted us to examine the expression of FoxE3 and Mab21l1, since mice with mutated FoxE3 or Mab21l1 have phenotypes that are similar to those of the PaxB transgenic mice, namely, a rudimentary lens and persistent connection between lens and cornea (Blixt et al, 2000;Yamada et al, 2003;Medina-Martinez et al, 2005). Moreover, it is known that the early expression of FoxE3 and Mab21l1 is downregulated in Sey mice and therefore dependent on Pax6 gene dosage (Yamada et al, 2003;Blixt et al, 2007).…”

Xhairy2 functions in Xenopus lens development by regulating p27xic1 expression

“…This might be related to the regulation of foxE3 expression by Xhairy2. FoxE3 is an important factor that regulates both proliferation and differentiation of lens cells in mice (Medina-Martinez et al, 2005). FoxE3 is also known to be important for lens morphogenesis in zebrafish (Shi et al, 2006).…”