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Inman, A.

Publications and source records attributed to Inman, A..

2 recordsLinked to original sources

A multi-tiered mechanical mechanism shapes the early neural plate

The formation of complex tissues during embryonic development requires an intricate spatiotemporal coordination of local mechanical processes regulating global tissue morphogenesis. Here, we uncover a novel mechanism that mechanically regulates the shape of the anterior neural plate (ANP), a vital forebrain precursor, during zebrafish gastrulation. Combining in vivo and in silico approaches we reveal that the ANP is shaped by global tissue flows regulated by distinct force generating processes. We show that mesendoderm migration and E-cadherin-dependent differential tissue interactions control distinct flow regimes in the neuroectoderm. Initial opposing flows lead to progressive tissue folding and neuroectoderm internalisation which in turn provide forces driving ANP tissue reshaping. We find that convergent extension is dispensable for internalisation but required for ANP tissue extension. Our results highlight how spatiotemporal regulation and coupling of different mechanical processes between tissues in the embryo controls the first folding event in the developing brain.

developmental biology↗

Translational control of furina by an RNA regulon is essential for heart morphogenesis and cardiac valve function

Heart development is a complex process, starting from specification of cardiac precursors and formation of a linear tube to gradual progression to a functional beating organ. For normal heart development, many processes, including asymmetric positioning of the heart along the left-right (L/R) axis, cardiac growth, and cardiac valve morphogenesis must be completed successfully. Although heart development has been studied extensively, the mechanisms that control heart morphogenesis and valve formation are not fully understood. The pro-convertase FurinA is a key protein that functions in heart development in many vertebrates including zebrafish. How FurinA activity is regulated during heart development is not known. Through computational analysis of the zebrafish transcriptome, we identified a short sequence and structure RNA motif in a variant transcript of FurinA harbouring a long 3untranslated region (3UTR). The alternative 3UTR furina isoform is expressed at embryonic stages preceding organ positioning. Reporter localization and RNA-binding assays show that the furina 3UTR forms complexes with the conserved RNA-binding protein and translational repressor Ybx1. Conditional mutant zebrafish embryos affecting ybx1 show premature and increased Furin reporter protein expression, abnormal cardiac morphogenesis and heart looping defects. Our mutant ybx1 hearts have an expanded atrioventricular canal, abnormal sino-atrial valves and many mutant embryos show retrograde blood flow from the ventricle to the atrium. This is similar to human heart valve regurgitation patients. Our findings show an essential function for the 3UTR element/Ybx1 regulon in translational repression of FurinA, revealing a new upstream regulatory mechanism that controls embryonic heart development, and demonstrates the ybx1 mutant as a model to study cardiac valve development and function.

developmental biology↗