Sang In Leea,1, Bo Ram Leea,1, Young Sun Hwanga, Hyung Chul Leea, Deivendran Rengaraja, Gwonhwa Songa, Tae Sub Parkb, and Jae Yong Hana,2
aWorld Class University Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Korea; and
bAvicore Biotechnology Institute, Optifarm Solution Inc., Gyeonggi-do 435-050, Korea
Edited by George Seidel, Colorado State University, Fort Collins, CO, and approved May 20, 2011 (received for review April 18, 2011)
MicroRNAs (miRNAs) play a critical role in determining the differentiation fate of pluripotent stem cells and germ cells in mammals. However, the mechanism(s) of miRNA-mediated posttranscriptional regulation with regard to lineage specification and differentiation in chick development require further investigation. Therefore, we conducted miRNA expression profiling to explore specific miRNA signatures in undifferentiated blastoderm and primordial germ cells (PGCs). We identified seven miRNAs that are highly expressed in blastoderm and 10 that are highly expressed in PGCs. In this study, miR-302a and miR-456 for blastoderm and miR-181a* for PGCs were analyzed further for their target transcripts and regulatory pathways. Both miR-302a and miR-456 bound directly to the sex-determining region Y box 11 transcript and could act as posttranscriptional coregulators to maintain the undifferentiated state of the chicken blastoderm through the suppression of somatic gene expression and differentiation. Moreover, miR-181a* showed a bifunctional role in PGCs by binding to two different transcripts. miR-181a* inhibited the somatic differentiation of PGCs by silencing homeobox A1 expression. Additionally, miR-181a* prevented PGCs from entering meiosis through the repression of the nuclear receptor subfamily 6, group A, member 1 transcript. Collectively, our data demonstrate that in chickens miRNAs intrinsically regulate the differentiation fate of blastoderms and PGCs and that the specific timing of germ cell meiosis is controlled through miRNA expression.
aves, germline, sex differentiation
1S.I.L. and B.R.L. contributed equally in this work.
2To whom correspondence should be addressed.
Author contributions: S.I.L., B.R.L., and J.Y.H. designed research; S.I.L., B.R.L., Y.S.H., H.C.L., and D.R. performed research; S.I.L., B.R.L., G.S., T.S.P., and J.Y.H. analyzed data; and S.I.L., B.R.L., D.R., G.S., T.S.P., and J.Y.H. wrote the paper.