Abstract
BackgroundCadherins are a superfamily of calcium-dependent adhesion molecules that play multiple roles in morphogenesis, including proliferation, migration, differentiation and cell-cell recognition. The subgroups of classic cadherins and δ-protocadherins are involved in processes of neural development, such as neurite outgrowth, pathfinding, target recognition, synaptogenesis as well as synaptic plasticity. We mapped the expression of 7 classic cadherins (CDH4, CDH6, CDH7, CDH8, CDH11, CDH14, CDH20) and 8 δ-protocadherins (PCDH1, PCDH7, PCDH8, PCDH9, PCDH10, PCDH11, PCDH17, PCDH18) at representative stages of retinal development and in the mature retina of the ferret by in situ hybridization.ResultsAll cadherins investigated by us are expressed differentially by restricted populations of retinal cells during specific periods of the ferret retinogenesis. For example, during embryonic development, some cadherins are exclusively expressed in the outer, proliferative zone of the neuroblast layer, whereas other cadherins mark the prospective ganglion cell layer or cells in the prospective inner nuclear layer. These expression patterns anticipate histogenetic changes that become visible in Nissl or nuclear stainings at later stages. In parallel to the ongoing development of retinal circuits, cadherin expression becomes restricted to specific subpopulations of retinal cell types, especially of ganglion cells, which express most of the investigated cadherins until adulthood. A comparison to previous results in chicken and mouse reveals overall conserved expression patterns of some cadherins but also species differences.ConclusionsThe spatiotemporally restricted expression patterns of 7 classic cadherins and 8 δ-protocadherins indicate that cadherins provide a combinatorial adhesive code that specifies developing retinal cell populations and intraretinal as well as retinofugal neural circuits in the developing ferret retina.
Highlights
Cadherins are a superfamily of calcium-dependent adhesion molecules that play multiple roles in morphogenesis, including proliferation, migration, differentiation and cell-cell recognition
We investigate the developmental expression of seven classic cadherins (CDH4, CDH6, CDH7, CDH8, CDH11, CDH14, CDH20) and eight δprotocadherins (PCDH1, PCDH7, PCDH8, PCDH9, PCDH10, PCDH11, PCDH17, PCDH18) in a single species, the ferret, by in situ hybridization
Each retinal layer is marked by the combinatorial expression of multiple classic and δ-protocadherins during development
Summary
Cadherins are a superfamily of calcium-dependent adhesion molecules that play multiple roles in morphogenesis, including proliferation, migration, differentiation and cell-cell recognition. The subgroups of classic cadherins and δ-protocadherins are involved in processes of neural development, such as neurite outgrowth, pathfinding, target recognition, synaptogenesis as well as synaptic plasticity. The mature neural retina comprises distinct sets of neurons, each with a characteristic morphology, location and connectivity. Together, they form a highly sophisticated network, arranged in distinct layers [reviewed in (page number not for citation purposes). Retinal development involves the processes of cellular proliferation, migration and differentiation. These processes are mediated by molecular mechanisms similar to those in the rest of the brain. Genes that play a role in retinogenesis include gene regulatory factors like the homeobox transcription factor Pax or the transcription factors MASH-1 and NeuroD, surface proteins like NgCAM or N-cadherin (cadherin-2), the Notch-Delta signaling pathway, diffusable factors like retinoic acid, sonic hedgehog or NGF, extracellular matrix molecules like β1integrins and synaptic adhesion molecules like sidekick, synaptophysin and synaptotagmin [reviewed in [4,5,6]]
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