PDCD10, the gene mutated in cerebral cavernous malformation 3, is expressed in the neurovascular unit.

Objective: Mutations in the programmed cell death 10 gene, PDCD10, cause the autosomal-dominant familial cerebral cavernous malformation 3 (CCM3). Little is known about the function of this gene in disease pathogenesis.

Methods: As a first step, we analyzed the messenger ribonucleic acid (mRNA) expression of CCM3 in the embryonic and postnatal mouse brain by in situ hybridization. We generated and characterized CCM3-specific polyclonal antibodies and analyzed CCM3 protein expression in human cerebral and solid organ (extracerebral) tissues using immunohistochemistry.

Results: In embryonic mouse brain, CCM3 mRNA is seen in the ventricular, subventricular, and intermediate zones, the cortical plate, the developing septum, striatum, midbrain, pons, cerebellum, and medulla. In the postnatal mouse brain, we detected CCM3/PDCD10 expression in the olfactory bulb, neocortex, striatum, septal nuclei, hippocampus, dentate gyrus, thalamic and hypothalamic nuclei, inferior colliculus, Purkinje and granule cell layers and deep nuclei of the cerebellum, and in many cells and nuclei in the medulla. Similar to CCM1 and CCM2, the CCM3/PDCD10 protein is expressed in the neurovascular unit but weakly in venous structures within cortical, subcortical, and brainstem tissue. CCM3/PDCD10 protein is strongly expressed in arterial endothelium but weakly or not at all in venous endothelium of extracerebral tissue.

Conclusion: The expression pattern of CCM3/PDCD10 in multiple organ systems displays similarities to CCM1 and CCM2. PDCD10/CCM3 is highly expressed in the neurovascular unit and in the arterial endothelium of structures within multiple organ systems, including the brain. These data provide additional information about CCM3 expression and its role in lesion development and pathogenesis.