Investigating the molecular guts of endoderm formation using zebrafish

Abstract

The vertebrate endoderm makes major contributions to the respiratory and gastrointestinal tracts and all associated organs. Zebrafish and humans share a high degree of genetic homology and strikingly similar endodermal organ systems. Combined with a multitude of experimental advantages, zebrafish are an attractive model organism to study endoderm development and disease. Recent functional genomics studies have shed considerable light on the gene regulatory programs governing early zebrafish endoderm development, while advances in biological and technological approaches stand to further revolutionize our ability to investigate endoderm formation, function and disease. Here, we discuss the present understanding of endoderm specification in zebrafish compared to other vertebrates, how current and emerging methods will allow refined and enhanced analysis of endoderm formation, and how integration with human data will allow modeling of the link between non-coding sequence variants and human disease.

Eomes function is conserved between zebrafish and mouse and controls left-right organiser progenitor gene expression via interlocking feedforward loops

“…Given that Eomesa is maternally contributed and not spatially restricted in early development ( Du et al, 2012 ), while accumulation of vgll4l activators is principally driven by Nodal at the dorsal margin, this suggests a model wherein Eomesa controls the specificity and timing of vgll4l induction. Eomesa mRNA steadily declines during blastula stages as expression of mixl1 , gata5 , tbx16 and sox32 increase, and is virtually undetectable at the onset of gastrulation, ( Figure 3A and Bruce et al, 2003 ; Figiel et al, 2021 ). While Eomesa protein does persist through gastrulation ( Du et al, 2012 ) it seems likely that temporal and spatial changes in abundance of vgll4l activators and repressors acting within these feedforward loops cooperatively regulate the specificity of vgll4l expression during DFC specification.…”

The molecular basis for functional divergence of duplicated SOX factors controlling endoderm formation and left-right patterning in zebrafish

“…An exception to this is sox32, which is hypothesised to have emerged through tandem duplication of Sox17 (Voldoire et al, 2017). While we and others have speculated that zebrafish Sox32 may function in similar processes to mammalian SOX17 (Figiel et al, 2021, Lilly et al, 2017), this has not been explored at the molecular level. Furthermore, it is unknown whether functions of the ancestral gene have been split among the two putative paralogues (sub-functionalisation) or whether they have functionally diverged post-duplication.…”