Developmental biology of the eye

Chapter 3 Developmental biology of the eye


Developmental biology provides an understanding of the mechanisms controlling the four-dimensional changes in shape (morphogenesis), cell type diversity (histogenesis), and functional maturation during embryogenesis and early development. Ocular development is a popular system for developmental biologists since the structure of the eye is similar throughout vertebrate evolution and the molecular basis of development is highly conserved in the well-studied invertebrate animal model, the fruit fly, Drosophila melanogaster.

For both ethical and technical reasons, experimental developmental biology is not possible in humans. This limitation is likely to change with the ability to induce trans-differentiation of adult human cells into induced pluripotent stems (iPS) cells.1 An ever-increasing understanding of the genetic basis of human malformations combined with the availability of patient-derived iPS cells predicts that human developmental biology will be an important and rapidly growing field. However, our current knowledge of eye development comes from Drosophila and vertebrate models: frogs (Xenopus laevus, Xenopus tropicalis), fish (zebrafish: Danio rerio, medaka: Oryzias latipes), chick (Gallus gallus), and mouse (Mus musculus). Each has strengths and weaknesses. For example, chick embryos have been extensively used for fate mapping (Box 3.1) and tissue recombination experiments, but there are few natural mutations available for study and genetic manipulation is difficult. In mice, it is possible to inactivate almost any gene in a targeted manner via homologous recombination (see Box 3.1) in embryonic stem cells, but very early development is difficult to visualize since this is a placental mammal. Although exact equivalence of animal model experimental data with orthologous processes in humans is unlikely given the expansion of gene families through evolutionary genome duplication and existence of species-specific phenomena, it is likely that many of the developmental mechanisms will be common and generalizable.

Box 3.1

Definition of terms

Domain − a specific region or amino acid sequence in a protein with a particular function

Fate mapping − a technique developed by Vogt to trace the specific regions of an early embryo

Gastrulation − process in early embryonic development whereby the single-layered blastula is reorganized into the trilaminar gastrula

Haploinsufficiency − the situation where an individual who is heterozygous for a certain gene mutation is clinically affected because a single copy of the gene is incapable of providing sufficient protein to maintain normal function

Homeobox − a short, usually highly conserved DNA sequence in various genes that encodes a homeodomain

Homeodomain − a domain in a protein that is encoded by a homeobox that recognizes and binds to specific DNA sequences in genes regulated by the homeotic gene

Homologous recombination − a type of genetic recombination in which nucleotide sequences are exchanged between two similar or identical molecules of DNA

Ligand − a signal-triggering molecule that binds to a site on a target protein

Morphogens − secreted proteins that organize surrounding tissues into distinct territories thus governing the pattern of tissue development

Morphogen gradients − morphogens produced from a defined localized source form a concentration gradient as they spread through the tissue. The graded signal acts directly on cells in a concentration-dependent fashion

Nodal proteins − a subset of transforming growth factor-beta (TGFβ) family responsible for mesoderm induction, patterning of the nervous system, and determination of dorsal-ventral axis in embryos

Nodal signaling − a signal transduction pathway involving nodal proteins which are essential in pattern formation and differentiation during embryogenesis

Notch signaling pathway − a cell signaling system important for cell−cell communication and involving gene regulation mechanisms that control multiple cell differentiation during embryonic and adult life

Null mutant − a mutation in a gene that leads to it not being transcribed into RNA and/or translated into a functional protein

Orthologous genes − genes in different species that are similar to each other because they originated by vertical descent from a single gene of the last common ancestor

Paralogue − a pair of genes that derive from the same ancestral gene

Sequence homology − situation where nucleic acid or protein sequences are similar because they have a common evolutionary origin

Signal transduction − process whereby an extracellular signaling molecule activates a membrane receptor that in turn alters intracellular molecules

Transcription − the process of creating a complementary RNA copy of a sequence of DNA. It is the first step leading to gene expression

Important concepts and processes in developmental biology


Signaling is one of the most important processes in developmental biology. It involves interaction of a ligand (see Box 3.1) with a receptor, which then effects a change, usually altering protein phosphorylation and/or the transcriptional (see Box 3.1) profile of the receptor-bearing cell. Ligands can be proteins (e.g. Sonic hedgehog) or small molecules (e.g. all-trans-retinoic acid). The receptors (e.g. fibroblast growth factor receptors) can be on the cell surface or intracellular (e.g. retinoic acid receptors). The ligand−receptor interaction often leads to a signal transduction (see Box 3.1) cascade (e.g. MAPK pathway). Some ligand−receptor interactions activate several different signal transduction pathways when the most commonly used pathway is known as canonical (e.g. beta catenin activation in Wnt signaling) and the alternative pathways known as non-canonical. There are many different signaling pathways used during eye development (Fig. 3.1).

Morphogen gradients (see Box 3.1) involve a diffusible ligand exerting concentration-dependent differential effects on target tissues. This important concept is summarized in the so-called French flag model (Fig. 3.2).

Jun 4, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on Developmental biology of the eye
Premium Wordpress Themes by UFO Themes