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Genesis 2020 Mar 01;583-4:e23354. doi: 10.1002/dvg.23354.
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miR-199 plays both positive and negative regulatory roles in Xenopus eye development.

Ritter RA , Ulrich CH , Brzezinska BN , Shah VV , Zamora MJ , Kelly LE , El-Hodiri HM , Sater AK .

To investigate microRNA (miR) functions in early eye development, we asked whether eye field transcription factors (EFTFs) are targets of miR-dependent regulation in Xenopus embryos. Argonaute (AGO) ribonucleoprotein complexes, including miRs and targeted mRNAs, were coimmunoprecipitated from transgenic embryos expressing myc-tagged AGO under the control of the rax1 promoter; mRNAs for all EFTFs coimmunoprecipitated with Ago in late neurulae. Computational predictions of miR binding sites within EFTF 3'UTRs identified miR-199a-3p ("miR-199") as a candidate regulator of EFTFs, and miR-199 was shown to regulate rax1 in vivo. Targeted overexpression of miR-199 led to small eyes, a reduction in EFTF expression, and reduced cell proliferation. Inhibition of interactions between mir-199 and the rax1 3'UTR reversed the small eye phenotype. Although targeted knockdown of miR-199 left the eye field intact, it reduced optic cup outgrowth and disrupted eye formation. Computational identification of candidate miR-199 targets within the Xenopus transcriptome led to the identification of ptk7 as a candidate regulator. Targeted overexpression of ptk7 resulted in abnormal optic cup formation and a reduction or loss of eye development, recapitulating the range of eye phenotypes seen following miR-199 knockdown. Our results indicate that miR-199 plays both positive and negative regulatory roles in eye development.

PubMed ID: 31909537
Article link: Genesis
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: elavl1 foxd4l1.1 gbx2 gmnn hace1 irx3 lhx2 mmut myc nr2e1 otx2 patz1 pax6 preb prox1 ptk7 rax six3 six6 sox11 ss18 tbx3 tp63 zbtb2 zic2
GO keywords: eye development

Phenotypes: WT + miR199 (Fig. 1 A-C) [+]

Article Images: [+] show captions