AUTHOR=Xing Cencan , Shen Weimin , Gong Bo , Li Yaqi , Yan Lu , Meng Anming 

TITLE=Maternal Factors and Nodal Autoregulation Orchestrate Nodal Gene Expression for Embryonic Mesendoderm Induction in the Zebrafish

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.887987

DOI=10.3389/fcell.2022.887987

ISSN=2296-634X

ABSTRACT=<p>Nodal proteins provide crucial signals for mesoderm and endoderm induction. In zebrafish embryos, the <italic>nodal</italic> genes <italic>ndr1</italic>/<italic>squint</italic> and <italic>ndr2</italic>/<italic>cyclops</italic> are implicated in mesendoderm induction. It remains elusive how <italic>ndr1</italic> and <italic>ndr2</italic> expression is regulated spatiotemporally. Here we investigated regulation of <italic>ndr1</italic> and <italic>ndr2</italic> expression using M<italic>hwa</italic> mutants that lack the maternal dorsal determinant Hwa with deficiency in β-catenin signaling, M<italic>eomesa</italic> mutants that lack maternal Eomesodermin A (Eomesa), M<italic>eomesa</italic>;M<italic>hwa</italic> double mutants, and the Nodal signaling inhibitor SB431542. We show that <italic>ndr1</italic> and <italic>ndr2</italic> expression is completely abolished in M<italic>eomesa</italic>;M<italic>hwa</italic> mutant embryos, indicating an essential role of maternal <italic>eomesa</italic> and <italic>hwa</italic>. Hwa-activated β-catenin signaling plays a major role in activation of <italic>ndr1</italic> expression in the dorsal blastodermal margin, while <italic>eomesa</italic> is mostly responsible for <italic>ndr1</italic> expression in the lateroventral margin and Nodal signaling contributes to ventral expansion of the <italic>ndr1</italic> expression domain. However, <italic>ndr2</italic> expression mainly depends on maternal <italic>eomesa</italic> with minor or negligible contribution of maternal <italic>hwa</italic> and Nodal autoregulation. These mechanisms may help understand regulation of Nodal expression in other species.</p>