Signaling and Gene Regulatory Networks in Mammalian Lens Development

Abstract

Ocular lens development represents an advantageous system to study regulatory mechanisms governing cell fate decisions, extracellular signaling, cell and tissue organization, and underlying gene regulatory networks. Spatiotemporaly regulated domains of BMP, FGF, and other signaling molecules in the late gastrula-early neurula stage embryos generate the border region between the neural plate and non-neural ectoderm from which multiple cell types, including lens progenitor cells, emerge and undergo initial tissue formation. Extracellular signaling and DNA-binding transcription factors govern lens and optic cup morphogenesis. Pax6, c-Maf, Hsf4, Prox1, Sox1, and a few additional factors regulate expression of the lens structural proteins, the crystallins. A multitude of cross-talks between a diverse array of signaling pathways control the complexity and order of the lens morphogenetic processes and its transparency.

Identification of Novel Gata3 Distal Enhancers Active in Mouse Embryonic Lens

“…4) and the Gata3 promoter (Fig. 4) (Cvekl and Zhang, 2017). Several binding sites for transcription factors implicated in lens Schematic representation of the 5-kb Gata3 promoter region and its adjacent loci (9230102O04Rik).…”

Zebrafish mab21l2 mutants possess severe defects in optic cup morphogenesis, lens and cornea development

“…Unlike in other vertebrates, where the developing lens pinches off from the surface ectoderm to form a hollow lens vesicle, the zebrafish lens develops as a mass of cells which remains attached to the surface ectoderm through much of its early development, until approximately 24 hours post fertilization (hpf) when it separates from the overlying surface ectoderm . This mass forms a solid spherical structure composed of cells which are becoming specified to either lens epithelial or lens fiber fates by means of the combined action of several signaling pathways (reviewed in Cvekl & Zhang, 2017) …”

Epha2 and Efna5 participate in lens cell pattern-formation

“…In mammals, the lens develops from a placode of head ectoderm under the influence of a paired box 6 (PAX6)-dependent gene regulatory network and several extracellular signaling pathways to form an exquisitely patterned, cellular structure composed of two cell types enclosed in a collagenous basement membrane or capsule. (Bassnett et al, 2011; Cheng et al, 2017b; Cvekl and Zhang, 2017). The anterior lens surface comprises a monolayer of mitotically competent epithelial cells that terminally differentiate at the lens equator into concentric layers (growthshells) of tightly packed, highly elongated, secondary fiber cells that form the refractive mass of the lens.…”

“…The anterior lens surface comprises a monolayer of mitotically competent epithelial cells that terminally differentiate at the lens equator into concentric layers (growthshells) of tightly packed, highly elongated, secondary fiber cells that form the refractive mass of the lens. Lens fiber cell formation is characterized by several unique re-modeling processes including accumulation of crystallins in the cytoplasm, remodeling of the cytoskeleton, specialization of the plasma-membrane, programmed loss of organelles, and formation of a core syncytium (Bassnett et al, 2011; Cheng et al, 2017b; Cvekl and Zhang, 2017). Collectively, these cellular processes are designed to establish and maintain lens transparency, minimize light scattering, and generate a high refractive index.…”