BMP/SMAD signaling promotes the synthesis and delivery of collagen (magenta) from deep inside the secretory network (yellow) of the skin into the cuticle, the worms’ most external layer which protects and gives shape to their bodies. Image credit: Jonathan Dietz and Christopher Rongo (CC BY 4.0)
Growth and development depend on the ability of cells to communicate through an intricate ballet of molecular signals that determine cell behaviors. Signaling proteins belonging to the BMP family, in particular, play an important role by activating certain ‘transcription factors’, known as Smad proteins, which then bind to specific DNA sequences to switch target genes on or off. The activity of these BMP-activated transcription factors is modulated by other molecular partners – Schnurri, for instance, is a well-known transcription factor partner of Smad. Still, exactly how Smad and Schnurri interact to control the expression of genes across the genome, and thereby execute complex biological programs, has remained unclear.
To investigate this question, Vora, Dietz et al. examined how Smad and Schnurri partner to regulate body size during the development of Caenorhabditis elegans, a transparent, non-parasitic worm widely used in research. Various genomic techniques were used to reveal where on the genome the transcription factors could bind, as well as to track resulting changes in gene expression. Software approaches were then adapted to combine these datasets, showing that Smad and Schnurri have both shared and independent targets. The two proteins usually cooperate to activate gene expression, but they sometimes antagonize each other’s functions. Finally, analyses showed that Smad and Schnurri help control body size by regulating the secretion of collagen. This protein is the primary component of the cuticle, a flexible external layer that shields the worms from the environment as well as determines their bodies’ shape and size. Overall, the work by Vora, Dietz et al. demonstrates that previous models for Smad and Schnurri interactions were incomplete, paving the way for further research into these proteins and their role in development.
