Mitral valve prolapse (MVP) is a common congenital valve disorder that has been linked to defects in primary cilia during cardiac development, yet the mechanisms connecting ciliary regulation to valvulogenesis remain incompletely understood. As DZIP1 is required for ciliogenesis and has been shown to be involved in MVP pathogenesis, we sought to identify interacting partners that may regulate its localization and function. Using an unbiased yeast two-hybrid screen of a human heart cDNA library, we identified BRD10, a previously uncharacterized bromodomain-containing protein, as a DZIP1-interacting partner. Co-immunoprecipitation confirmed the DZIP1–BRD10 interaction and mapped the binding region to a conserved domain containing a putative nuclear localization sequence. RNAscope and immunofluorescence demonstrated that BRD10 and DZIP1 are co-expressed in developing murine valve cells, with BRD10 localizing near the basal body and transition zone of the primary cilium. BRD10 also interacted with acetylated α-tubulin, supporting a relationship with ciliary microtubule structures. Nuclear–cytoplasmic fractionation further showed that BRD10 promotes cytoplasmic enrichment of DZIP1. Together, these findings identify BRD10 as a novel regulator of DZIP1 subcellular localization and suggest that bromodomain-mediated recruitment at the primary cilium may contribute to normal valvulogenesis and developmental mechanisms relevant to MVP.

Van Maldergem Syndrome (VMS) is a rare autosomal recessive disorder caused by pathogenic variants in the atypical cadherin genes DCHS1 or FAT4 and is marked by craniofacial, skeletal, and neurodevelopmental abnormalities. Although DCHS1–FAT4 binding is mediated by their respective extracellular domains, the in vivo function of the DCHS1 intracellular domain (ICD) is poorly defined. To test its function, we generated mice in which the DCHS1 ICD was deleted and replaced with a V5 epitope tag (Dchs1^ΔICD-V5). Homozygous Dchs1^{ΔICD-V5/ΔICD-V5} mice are viable but exhibit VMS-like craniofacial flattening with enlarged fontanelles and reduced palatine/maxillary structures, along with airway cartilage abnormalities including reduced mineralization and decreased tracheal circularity. In periventricular regions, wild-type DCHS1 expression shows polarized localization, whereas mice with the ICD deletion exhibit altered cell polarization within the subventricular zone, concomitant with changes in neural cellular distribution. Neonatal brains display reduced pYAP1: YAP1 ratios and increased Ki67+ proliferation with greater Ki67–neuronal co-localization within the periventricular zone. Together, these data identify the DCHS1 ICD as a critical effector for DCHS1 signaling and a regulator of polarity-dependent growth, with associated changes in Hippo pathway activity during craniofacial and neural morphogenesis. Additionally, our data establish Dchs1^{ΔICD-V5/ΔICD-V5} mice as a model that recapitulates core features of VMS, thereby allowing new mechanistic discoveries into its pathogenesis.