PgmNr Z6043: Cartilage development requires the function of Estrogen-related receptor alpha that directly regulates sox9 expression in zebrafish.

Authors:
Y. Kim; S. Bhandari; I. Nam; K. Yoo; R. Park; S. Choe


Institutes
center for metabolic function regulation, Wonkwang Univ, Iksan, Jeonbuk, KR.


Abstract:

Estrogen related receptor alpha (ESRRa) regulates a number of cellular processes including development of bone and muscles. However, direct evidence regarding its involvement in cartilage development remains elusive. In this report, we establish an in vivo role of ESRRa in cartilage development during embryogenesis in zebrafish. Gene expression analysis indicates that esrra is expressed in developing pharyngeal arches where genes necessary for cartilage development are also expressed. Loss of function analysis shows that knockdown of esrra impairs expression of both sox9 and col2a1 and thus induces abnormally formed cartilage in pharyngeal arches. Importantly, we identify putative ESRRa binding elements in upstream regions of sox9 to which ESRRa can directly bind, indicating that ESRRa may directly regulate sox9 expression. Accordingly, ectopic expression of sox9 rescues defective formation of cartilage induced by the knockdown of esrra. Taken together, our results indicate for the first time that ESRRa is essential for cartilage development by regulating sox9 expression during vertebrate development.