DOI: 10.1101/469239Nov 13, 2018Paper

A Scube2-Shh feedback loop links morphogen release to morphogen signaling to enable scale invariant patterning of the ventral neural tube

BioRxiv : the Preprint Server for Biology
Zach CollinsSean G Megason


To enable robust patterning, morphogen systems should be resistant to variations in gene expression and tissue size. Here we explore how a Shh morphogen gradient in the ventral neural tube enables proportional patterning in embryos of varying sizes. Using a surgical technique to reduce the size of zebrafish embryos and quantitative confocal microscopy, we find that patterning of neural progenitors remains proportional after size reduction. Intriguingly, a protein necessary for Shh release, Scube2, is expressed far from the source of sonic hedgehog production. scube2 expression levels control Shh signaling extent during ventral neural patterning and conversely Shh signaling represses the expression of scube2, thereby restricting its own signaling. scube2 is disproportionately downregulated in size-reduced embryos, providing a potential mechanism for size-dependent regulation of Shh. This regulatory feedback is necessary for pattern scaling, as demonstrated by a loss of scaling in scube2 overexpressing embryos. In a manner akin to the expander-repressor model of morphogen scaling, we conclude that feedback between Shh signaling and scube2 expression enables proportional patterning in the ventral neural tube by encoding a tissue s...Continue Reading

Related Concepts

Diagnostic Techniques, Surgical
Gene Expression
Neural Tube
Microscopy, Confocal
Neural Stem Cells
BMP Receptor Signaling Pathway

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