The effect of Activin pathway modulation on the expression of both pluripotency and differentiation markers during early zebrafish development compared with other vertebrates

• Published in: Journal of experimental zoology. Part B, Molecular and developmental evolution Molecular and developmental evolution, 2021-11, Vol.336 (7), p.562-575
• Main Authors: Hasanpour, Shaghayegh, Eagderi, Soheil, Poorbagher, Hadi, Angrand, Pierre‐Olivier, Hasanpour, Mohammad, Lashkarbolok, Maryam
• Format: Article
• Language: English
• Subjects: Activins - metabolism; activin‐like factors; Animals; Antigens, Differentiation - genetics; differentiation; Intracellular Signaling Peptides and Proteins; Life Sciences; Nanog Homeobox Protein; Nodal Signaling Ligands; Octamer Transcription Factor-3; pluripotency; SOXF Transcription Factors; Transcription Factors; zebrafish; Zebrafish - growth & development; Zebrafish Proteins - genetics
• ISSN: 1552-5007; 1552-5015
• DOI: 10.1002/jez.b.23070

Activin‐like factors control many developmental processes, including pluripotency maintenance and differentiation. Although Activin‐like factors' action in mesendoderm induction has been demonstrated in zebrafish, their involvement in preserving the stemness remains unknown. To investigate the role of maternal Activin‐like factors, their effects were promoted or blocked using synthetic human Activin A or SB‐431542 treatments respectively until the maternal to zygotic transition. To study the role of zygotic Activin‐like factors, SB‐431542 treatment was also applied after the maternal to zygotic transition. The effect of the pharmacological modulations of the Activin/Smad pathway was then studied on the mRNA expressions of the ndr1, ndr2, tbxta (no tail/ntl) as the differentiation index, mych, nanog, and oct4 (pou5f3) as the pluripotency markers of the zebrafish embryonic cells as well as sox17 as a definitive endoderm marker. Expression of the target genes was measured at the 16‐cell, 256‐cell, 1K‐cell, oblong, dome, and shield stages using the real‐time quantitative polymerase chain reaction (RT‐qPCR). Activation of the maternal Activin signaling pathway led to an increase in zygotic expression of the tbxta, particularly marked at the oblong stage. In other words, promotion of the maternal Activin/Smad pathway induced differentiation by advancing the major peaks of ndr1 and nanog, thereby eliciting tbxta expression. Whereas suppression of the maternal or zygotic Activin/Smad pathway sustained the pluripotency by preventing the major peaks of ndr1 and nanog as well as tbxta encoding. Promotion of the maternal Activin/Smad pathway using Activin induced differentiation by advancing the major peaks of ndr1 and nanog, thereby eliciting tbxta expression, whereas suppression of the maternal or zygotic Activin/Smad pathway through SB‐431542 administration sustained the pluripotency by preventing the major peaks of ndr1 and nanog as well as tbxta encoding. Research highlights Activin‐like factors promote the key pluripotency factors expression and a wide range of endodermal genes in zebrafish as well as mammals. Activin‐like factors maintain the pluripotent state or drive the development along the mesendodermal pathways in zebrafish as well as mammals.