Abstract
Purpose: :
Retinal neurons extend their dendritic fields to achieve a degree of dendritic overlap with homotypic neighbors that is specific for each cell type, while their primary dendrites exhibit a characteristic higher order branching where they receive innervation from their afferents. How these nerve cells regulate their dendritic growth and morphology is unclear, but evidence in favor of cell–intrinsic specification, as well as for environmental regulation by neighboring cells, has recently been published.
Methods: :
We have employed the Cre–loxP system to conditionally inactivate Lim1 function in order to examine these possibilities in developing horizontal cells. Using the Six3 promoter (Furuta et al., 2000) to drive Cre recombinase expression within the developing retina, Lim1 function was ablated within a subset of horizontal cells that in turn fail to migrate to the horizontal cell layer and differentiate normally (see abstract by R. Poché).
Results: :
The remaining horizontal cells that are properly localized adjacent to the outer plexiform layer (being about half of the normal population in these mice) differentiate a dendritic morphology that is essentially normal. However, the dendritic field has nearly doubled in size. Such larger horizontal cells should sample from a correspondingly larger retinal area thereby receiving innervation from twice their normal afferent number. In fact, the dendritic fields of these horizontal cells now exhibit significantly more dendritic branches and terminal clusters, the latter being indicative of sites of contact with individual cone pedicles, than they would normally differentiate.
Conclusions: :
These results provide strong support for the claim that the dendritic field size of retinal horizontal cells is regulated by interactions with homotypic neighbors, while afferent number instructs the differentiation of terminal clustering within the dendritic field.
Keywords: horizontal cells • differentiation • retinal connections, networks, circuitry