Disease relevance of CadN

• This novel HMR-1 isoform is very similar to DN-cadherin, and a mutant strain that specifically lacks the function of this isoform displays defects in the fasciculation and outgrowth of a subset of motor neuron processes; a phenotype that resembles loss of DN-cadherin function in Drosophila [1].

High impact information on CadN

• The classic cadherin N-cadherin is involved in stabilization of dendritic spines and branches [2].
• Drosophila N-cadherin mediates an attractive interaction between photoreceptor axons and their targets [3].
• We propose that N-cadherin mediates a homophilic, attractive interaction between photoreceptor growth cones and their targets that precedes synaptic partner choice [3].
• Using a panel of ORN subclass-specific markers, we demonstrate that in the adult AL, N-cadherin (N-cad) mutant ORN terminals remain segregated from dendrites of target neurons [4].
• Although the N-cadherin locus potentially encodes eight alternatively spliced isoforms, transgenic expression of one isoform is sufficient to rescue all phenotypes [5].

Biological context of CadN

• CadN alternative splicing might provide a novel mechanism to fine-tune its adhesive activity at different developmental stages or to restrict the use of high-affinity 18b-type isoforms at the adult stage [6].
• In vitro quantitative cell aggregation assays revealed that all CadN isoforms mediate homophilic interactions, but the isoforms encoded by exon 18b have a higher adhesive activity than those by its alternative, 18a [6].
• The CadN locus contains three modules of alternative exons (7a/b, 13a/b, and 18a/b) and undergoes alternative splicing to generate multiple isoforms [6].
• Because Liprin-alpha, the receptor tyrosine phosphatase LAR, and N-cadherin share qualitatively similar mutant phenotypes in R1-R6 cells and are coexpressed in R cells and their synaptic targets, we infer that these three genes act at the same step in the targeting process [7].
• Cooperative activities of Drosophila DE-Cadherin and DN-Cadherin regulate the cell motility process of ommatidial rotation [8].

Anatomical context of CadN

• DE- and DN-cadherin show complementary expression patterns in the presumptive ectoderm and mesoderm at the mRNA level [9].
• We found that switching of cadherin expression from the DE- to the DN-type in the mesodermal germ layer occurred downstream of the mesoderm-determination genes twist and snail [9].
• In the Drosophila visual system, N-cadherin is required in both photoreceptor (R cell) axons and their targets to mediate stabilizing interactions required for R cell target selection [7].
• Thus, these two proteins, unlike N-cadherin, are functionally asymmetric between axons and dendrites [7].
• N-cadherin is also essential for the development of PN axon terminal arbors in two distinct central targets: regulating branch stability in the lateral horn and restricting high-order branching in the mushroom body [5].

Other interactions of CadN

• A recent series of genetic studies in the Drosophila visual system has demonstrated roles for several cell adhesion molecules, including N-cadherin and the receptor protein tyrosine phosphatase LAR in proper synaptic targeting of photoreceptor axons [10].

References