Growth factor regulation of lens development

Abstract

Lens arises from ectoderm situated next to the optic vesicles. By thickening and invaginating, the ectoderm forms the lens vesicle. Growth factors are key regulators of cell fate and behavior. Current evidence indicates that FGFs and BMPs are required to induce lens differentiation from ectoderm. In the lens vesicle, posterior cells elongate to form the primary fibers whereas anterior cells differentiate into epithelial cells. The divergent fates of these embryonic cells give the lens its distinctive polarity. There is now compelling evidence that, at least in mammals, FGF is required to initiate fiber differentiation and that progression of this complex process depends on the synchronized and integrated action of a number of distinct growth factor-induced signaling pathways. It is also proposed that an antero-posterior gradient of FGF stimulation in the mammalian eye ensures that the lens attains and maintains its polarity and growth patterns. Less is known about differentiation of the lens epithelium; however, recent studies point to a role for Wnt signaling. Multiple Wnts and their receptors are expressed in the lens epithelium, and mice with impaired Wnt signaling have a deficient epithelium. Recent studies also indicate that other families of molecules, that can modulate growth factor signaling, have a role in regulating the ordered growth and differentiation of the lens.

Function and biological roles of the Dickkopf family of Wnt modulators

“…These Dkks display suggestive expression patterns in eye primordia, including pigmented epithelium, choroid and retina (Monaghan et al, 1999). Wnt/b-catenin signaling plays an important role in various stages of eye formation, including early patterning (Esteve and Bovolenta, 2006), retinal development (Van Raay and Vetter, 2004), lens formation (Lovicu and McAvoy, 2005) and eye angiogenesis (Niehrs, 2004a). In humans, loss of LRP5 function causes congenital blindness (pseudoglioma) (Gong et al, 2001).…”

GAD isoforms exhibit distinct spatiotemporal expression patterns in the developing mouse lens: Correlation with Dlx2 and Dlx5

“…3B,C). At E12.5, strong staining was observed in both the posterior wall, containing elongating primary fibers and epithelial cells at the anterior pole, which remain undifferentiated and retain their proliferation capacity (McAvoy et al, 1999;Menko, 2002;Lovicu and McAvoy, 2005).…”

“…Thereafter, mitotically active cells near the equatorial region (termed germinative epithelium) divide and migrate toward the equator, where they elongate and differentiate into secondary lens fiber cells, a process continuing throughout life (McAvoy, 1978;Lovicu and McAvoy, 2005). From E14.5 on, GAD67 expression was localized in both primary and secondary fiber cells, with the strongest labeling at E16.5-E17.5 (Fig.…”

“…The lens derives from a thickening of the surface ectoderm, the lens placode, at around embryonic day (E) 9.5 (for recent review on lens development, refer to Piatigorsky, 1981;McAvoy et al, 1999;Menko, 2002;Lovicu and McAvoy, 2005). As differentiation proceeds, the presumptive lens ectoderm invaginates to first form the lens cup (lens pit) at E10.5 and subsequently the lens vesicle (at E11.5), which is composed of a single layer of epithelial cells.…”

Isolation and characterization of a novel gene, xMADML, involved in Xenopus laevis eye development

“…Its development is directed by means of inductive interactions from specific tissues derived from all embryonic germ layers. Although several genes involved in eye development have been characterized to date, there are still many gaps in our understanding of the molecular pathways involved in this process (reviewed in Fini et al, 1997;Perron et al, 1998;Chow and Lang, 2001;Hanson, 2001;Graw and Loster, 2003;Zuber et al, 2003;Lovicu and McAvoy, 2005).…”