MicroRNA-206 Regulates Cell Movements during Zebrafish Gastrulation by Targeting <i>prickle1a</i> and Regulating c-Jun N-Terminal Kinase 2 Phosphorylation

Abstract

During vertebrate gastrulation, both concurrent inductive events and cell movements are required for axis formation. Convergence and extension (CE) movements contribute to narrowing and lengthening the forming embryonic axis. MicroRNAs (miRNAs) play a critical role in regulating fundamental cellular functions and developmental processes, but their functions in CE movements are not well known. Zebrafish mir206 is maternally expressed and present throughout blastulation and gastrulation periods. Either gain or loss of function of mir206 leads to severe defects of convergent extension movements both cell autonomously and non-cell autonomously. Mosaic lineage tracing studies reveal that the formation of membrane protrusions and actin filaments is disturbed in mir206-overexpressing embryos or mir206 morphants. Mechanistically, mir206 targets prickle1a (pk1a) mRNA and as a result regulates c-Jun N-terminal protein kinase 2 (JNK2) phosphorylation. pk1a overexpression or knockdown can rescue convergent extension defects induced by mir206 overexpression or knockdown, respectively. Therefore, mir206 is an essential, novel regulator for normal convergent and extension movements by regulating mitogen-activated protein kinase (MAPK) JNK signaling.