Patterning the dorsal-ventral axis of the vertebrate retina.

摘要

The vertebrate eye is a highly organized sensory organ designed to receive, integrate and transmit visual information. The molecular mechanisms that establish the dorsal-ventral (D-V) axis of the eye are largely unknown. The timing of the determination of the D-V axis was estimated using a series of ablation experiments. After removal of the dorsal eye primordium at Hamburger Hamilton (HH) stage 10–11, the D-V restriction of molecular and cell fate markers was maintained. Therefore, the D-V axis has not been fixed at this developmental stage. The expression of two homeobox genes, cVax and mVax2, in the ventral region of the early eye led us to determine their functional role in specification of ventral positional identity. Retroviral misexpression of both Vax genes ventralized the expression of several dorsally or ventrally restricted molecular markers. Projections of the dorsal retinal ganglion cells were profoundly aberrant following forced expression of cVax while the ventral ganglion cells' projections were not altered. Thus, Vax genes are key regulators of D-V retinal positional identity.; Distinct domains of gene expression along the D-V retinal axis emerge coincident with the determination of the axis. The domains are characterized by expression of several different genes and persist from optic cup stages into late retinogenesis. Some of these molecules have been shown to maintain and/or establish compartment boundaries in the chick hindbrain. To determine whether the expression domains are classical lineage restriction compartments, a retroviral lineage tracing study was performed. This study revealed a strong tendency of clones at the borders of expression domains to remain within their expression domains. Only 20% of the clones cross the borders of gene expression whereas 57% of the clones cross an arbitrary border within the same region. Thus, the proliferation and migratory properties of cells within this retinal region probably do not account for the observed restriction of clones. The discovery of restricted gene expression domains and identification of key molecular players has elucidated the patterning of the D-V axis of the neural retina.