RT Journal Article
SR Electronic
T1 <em>Bicc1</em> and <em>dicer</em> regulate left-right patterning through post-transcriptional control of the Nodal-inhibitor <em>dand5</em>
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.29.924456
DO 10.1101/2020.01.29.924456
A1 Markus Maerker
A1 Maike Getwan
A1 Megan E. Dowdle
A1 José L. Pelliccia
A1 Jason C. McSheene
A1 Valeria Yartseva
A1 Katsura Minegishi
A1 Philipp Vick
A1 Antonio J. Giraldez
A1 Hiroshi Hamada
A1 Rebecca D. Burdine
A1 Michael D. Sheets
A1 Axel Schweickert
A1 Martin Blum
YR 2020
UL http://biorxiv.org/content/early/2020/01/29/2020.01.29.924456.abstract
AB Rotating cilia at the vertebrate left-right organizer (LRO) generate an asymmetric leftward flow, which is sensed by cells at the left LRO margin. How the flow signal is processed and relayed to the laterality-determining Nodal cascade in the left lateral plate mesoderm (LPM) is largely unknown. We previously showed that flow down-regulates mRNA expression of the Nodal inhibitor Dand5 in left sensory cells. De-repression of the co-expressed Nodal drives LPM Nodal cascade induction. Here, we identify the mechanism of dand5 downregulation, finding that its posttranscriptional repression is a central process in symmetry breaking. Specifically, the RNA binding protein Bicc1 interacts with a proximal element in the 3’-UTR of dand5 to repress translation in a dicer1-dependent manner. The bicc1/dicer1 module acts downstream of flow, as LRO ciliation was not affected upon its loss. Loss of bicc1 or dicer1 was rescued by parallel knockdown of dand5, placing both genes in the process of flow sensing.