LAUSR

Nonsyndromic microtia is a kind of congenital ear malformation with unclear pathogenic genes. Cadherin-11 (CDH11, OB-cadherin) is a member of the cadherin family, which has been demonstrated to play important roles in controlling morphogenesis and cell biological characteristics during multiple developmental processes. In the present study, we found low expression of CDH11 in microtia cartilage compared with the normal one for the first time. For a more comprehensive and in-depth understanding of CDH11 in microtia development, we performed both gain- and loss-of-function experiments to detect the effect of CDH11 on chondrocytes. CDH11 promoted chondrocyte proliferation by increasing S-phase cell numbers and increasing cell migration, which is important for tissue morphogenesis. Additionally, knockdown of CDH11 in chondrocytes reduced the quality of engineered cartilage by decreasing the key transcription factors of chondrogenesis, SOX9 expression, and cartilage ECM production, including collagen type II (COL2A) and elastin (ELN), compared to the control group. Furthermore, RNA-Seq on CDH11 knockdown chondrocytes showed that it was highly related to HOX family genes, which have been reported to be important regulatory genes patterning craniofacial tissue formation. This study identified CDH11 as a candidate pathogenic gene of microtia and supported the potential key role of CDH11 in craniofacial malformations.