Work

Proteolytic Restriction of Chordin Range Underlies BMP Gradient Formation

Year: 2020

Type: article

Abstract: A fundamental question in developmental biology is how morphogens, such as bone morphogenetic protein (BMP), form precise signaling gradients to impart positional and functional identity to the cells of the early embryo. We combine rigorous mutant analyses with quantitative immunofluorescence to determine that the proteases Bmp1a and Tolloid spatially restrict the BMP antagonist Chordin in dorsoventral (DV) axial patterning of the early zebrafish gastrula. We show that maternally deposited Bmp1a plays an unexpected and non-redundant role in establishing the BMP signaling gradient, while the Bmp1a/Tolloid antagonist Sizzled is surprisingly dispensable. Combining computational modeling and in vivo analyses with an immobile Chordin construct, we demonstrate that long-range Chordin diffusion is not necessary for BMP gradient formation and DV patterning. Our data do not support a counter-gradient of Chordin and instead favor a Chordin sink, established by Bmp1a and Tolloid, as the primary mechanism that drives BMP gradient formation.

Source: Cell Reports

DOI: 10.1016/j.celrep.2020.108039

Authors: Francesca B. Tuazon, Xu Wang, Jonathan Lee Andrade, David Umulis, Mary C. Mullins

Institutions: University of Pennsylvania, Purdue University West Lafayette

Language: English

Topic: Developmental Biology and Gene Regulation

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $5,200

Funders: National Institutes of Health, National Institute of General Medical Sciences, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development