Abstract
In many vertebrates, establishment of Left-Right (LR) asymmetry results from the activity of a ciliated organ functioning as the LR Organizer (LRO). While regulation of the formation of this structure by major signaling pathways has been described, the transcriptional control of LRO formation is poorly understood. Using the zebrafish model, we show that the transcription factors and cofactors mediating or regulating the transcriptional outcome of the Hippo signaling pathway play a pivotal role in controlling the expression of genes essential to the formation of the LRO including ligands and receptors of signaling pathways involved in this process and most genes required for motile ciliogenesis. Moreover, the transcription cofactor, Vgll4l regulates epigenetic programming in LRO progenitors by controlling the expression of writers and readers of DNA methylation marks. Altogether, our study uncovers a novel and essential role for the transcriptional effectors and regulators of the Hippo pathway in establishing LR asymmetry.
Highlights
Formation of organs during embryonic development requires a progressive restriction of lineage potential
To identify novel factors involved in the transcriptional regulation of the formation of the Left-Right Organizer (LRO) we screened the zebrafish gene expression patterns database for transcription factor (TF) or TcoFs expressed in the Kupffer’s vesicle (KV) and/or in its progenitors
We identified Vestigial like 4 like (Vgll4l), a TcoF member of the Vestigial like four family, which is strongly expressed at gastrula stage in LRO progenitors (Figure 1A)
Summary
Formation of organs during embryonic development requires a progressive restriction of lineage potential. The KV is the fish homolog of the ventral node of the mouse, the Xenopus gastrocoel roof plate and the notochordal plate in rabbit This organ is composed of ~50 monociliated cells organized as a hollow sphere with motile cilia facing its lumen. Rotation of these cilia generates a transient counterclockwise fluid flow that directs asymmetric activation of a conserved Nodal signaling pathway that guides asymmetric morphogenesis of developing organs (Dasgupta and Amack, 2016).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
