Odd skipped related 1 is a negative feedback regulator of nodal‐induced endoderm development. Issue 12 (18th October 2014)

• Record Type: Journal Article
• Authors: Terashima, Alexandra V.; Mudumana, Sudha P.; Drummond, Iain A.
• Is Part Of: Developmental dynamics. Volume 243:Issue 12(2014:Dec.)
• Page Start: 1571
• Page End: 1580
• Publication Date: 2014-10-18
• Subjects: Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.24191
• Languages: English
• ISSNs: 1058-8388

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p> <underline>Background</underline> <underline>:</underline> Early embryo patterning is orchestrated by tightly regulated morphogen gradients. The Nodal morphogen patterns the mesendoderm, giving rise to all endoderm and head and trunk mesoderm. High Nodal concentrations favor endoderm differentiation while lower promote mesoderm differentiation. Nodal signaling is controlled by both positive and negative feedback regulation to ensure robust developmental patterning. <underline>Results:</underline> Here we identify <italic>odd skipped related 1 (osr1)</italic>, a zinc finger transcription factor, as a new element in Nodal feedback regulation affecting endoderm development. We show that <italic>osr1</italic> expression in zebrafish germ ring mesendoderm requires Nodal signaling; <italic>osr1</italic> expression was lost in embryos lacking Nodal signaling. Conversely, <italic>osr1</italic> expression was ectopically induced by the activation of Nodal signaling. Furthermore we demonstrate that <italic>osr1</italic> responds directly to Nodal signaling. Additionally, <italic>osr1</italic> knockdown generated excess endoderm cells marked by <italic>sox32</italic> expression while expression of <italic>osr1</italic> mRNA was not affected in <italic>sox32</italic>‐deficient embryos. <underline>Conclusions:</underline> Our findings identify <italic>osr1</italic> as a Nodal‐induced, negative feedback regulator of Nodal signaling that acts at the earliest stages of endoderm differentiation to limit the number of endoderm progenitors. As such, we propose that <italic>osr1</italic> represents a novel network motif controlling the output of Nodal signaling to regulate mesendoderm patterning. <italic>Developmental Dynamics 243:1571–1580, 2014</italic>. © 2014 Wiley Periodicals, Inc.</p> </abstract>