Biology subjects

Forbes-Beadle, L.

Publications and source records attributed to Forbes-Beadle, L..

2 recordsLinked to original sources

bioRxiv2024

An avidity-driven mechanism of extracellular BMP regulation by Twisted gastrulation

During dorsoventral patterning of bilaterian embryos, the conserved regulator Twisted gastrulation (Tsg) modulates BMP signalling by binding Chordin/Short gastrulation (Sog). Here we elucidate the mechanism by which Tsg interacts with Sog/Chordin to promote formation of the inhibitory Tsg-Sog/Chordin-BMP complex and regulate BMP signalling extracellularly. We identify and validate in vitro a hydrophobic interface in the Tsg C-terminal domain that binds Chordin. Mutation of this epitope in Drosophila Tsg (TsgL100A) results in an unexpectedly mild perturbation to embryonic BMP gradient formation. We show that a protosome-specific Tsg C-terminal extension also binds Sog, and the presence of this second binding site allows partial rescue of Sog interaction with TsgL100A in the presence of BMP. Consistent with this, a truncated Tsg protein lacking both Sog binding regions is unable to support BMP gradient formation in vivo. As our data show that disruption of either Sog binding site in Tsg, but not both, can be overcome by Tsg-BMP and Sog-BMP interactions, we present a new avidity-driven mechanism of BMP gradient formation that will be relevant to a broad range of developmental contexts. Summary statementIdentification and mutational analysis of the binding epitopes that mediate Twisted gastrulation interaction with Short gastrulation/Chordin reveals an avidity-based model of embryonic BMP gradient formation.

developmental biology↗

bioRxiv2020

Insulin-like signalling influences the coordination of Drosophila larval hemocyte number with body size

Blood cells, known as hemocytes in invertebrates, play important and conserved roles in immunity, wound healing and tissue remodelling. The control of hemocyte number is therefore critical to ensure these functions are not compromised, and studies using Drosophila are proving useful for understanding how this occurs. Recently, the well characterised embryonic patterning gene, torso-like (tsl), was identified as being required both for normal hemocyte number and for providing immunity against certain pathogens. Here, we report that Tsl is required specifically during the larval phase of hematopoiesis, and that the reduced hemocyte number found in tsl mutant larvae is likely the result of a reduced larval growth rate and compromised insulin signalling. Consistent with this, we find that impairing insulin-mediated growth, either by nutrient deprivation or genetically, results in fewer hemocytes. This is likely the result of impaired insulin-like signalling in the hemocytes themselves since modulation of Insulin-like Receptor (InR) activity specifically in hemocytes causes concomitant changes to their population size in developing larvae. Taken together, our work reveals the strong relationship that exists between body size and hemocyte number, and suggests that insulin-like signalling contributes to, but is not solely responsible for, keeping these tightly aligned during larval development.

genetics↗