KCTD10 is critical for heart and blood vessel development of zebrafish

Abstract

KCTD10 is a member of the PDIP1 family, which is highly conserved during evolution, sharing a lot of similarities among human, mouse, and zebrafish. Recently, zebrafish KCTD13 has been identified to play an important role in the early development of brain and autism. However, the specific function of KCTD10 remains to be elucidated. In this study, experiments were carried out to determine the expression pattern of zebrafish KCTD10 mRNA during embryonic development. It was found that KCTD10 is a maternal gene and KCTD10 is of great importance in the shaping of heart and blood vessels. Our data provide direct clues that knockdown of KCTD10 resulted in severe pericardial edema and loss of heart formation indicated by morphological observation and crucial heart markers like amhc, vmhc, and cmlc2. The heart defect caused by KCTD10 is linked to RhoA and PCNA. Flk-1 staining revealed that intersomitic vessels were lost in the trunk, although angioblasts could migrate to the midline. These findings could be helpful to better understand the determinants responsible for the heart and blood vessel defects.

The Cullin-3–Rbx1–KCTD10 complex controls endothelial barrier function via K63 ubiquitination of RhoB

“…We found KCTD10 to be most relevant as substrate receptor for the ubiquitination and degradation of RhoB. KCTD10 contains a BTB/POZ domain and regulates cardiovascular development in zebrafish and mouse ( Hu et al, 2014 ; Ren et al, 2014 ; Tong et al, 2014 ). Although different substrates were proposed to mediate the effects of loss of KCTD10 in these animal models, RhoGTPases were suggested as potential targets of KCTD10 in regulation of cardiovascular development.…”

Genes regulated by potassium channel tetramerization domain containing 15 (Kctd15) in the developing neural crest

“…Other family members appear to have very different molecular functions by acting in the regulation of transcription. These include Kctd10, a factor involved in heart development through the inhibition of Tbx5a activity, apparently by direct interaction between the Tbx and Kctd components (Hu et al, 2014; Tong et al, 2014). In addition Kctd10 also interacts with proliferating cell nuclear antigen and through this interaction affects proliferation (Wang et al, 2009).…”

Rho GTPases Signaling in Zebrafish Development and Disease

“…rhoa mRNA overexpression rescued heart defects observed in kctd10 (Potassium Channel Tetramerization Domain containing 10) morphants; the latter is a member of the polymerase delta-interacting protein 1 (PDIP1). KCTD10 causes RhoA degradation, a step required for normal cardiogenesis that is likely to be conserved among vertebrates [93].…”