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Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids
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Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids
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Journal Article
Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids
2022
Overview
Morphogens are signaling molecules that convey positional information and dictate cell fates during development. Although ectopic expression in model organisms suggests that morphogen gradients form through diffusion, little is known about how morphogen gradients are created and interpreted during mammalian embryogenesis due to the combined difficulties of measuring endogenous morphogen levels and observing development in utero. Here we take advantage of a human gastruloid model to visualize endogenous Nodal protein in living cells, during specification of germ layers. We show that Nodal is extremely short range so that Nodal protein is limited to the immediate neighborhood of source cells. Nodal activity spreads through a relay mechanism in which Nodal production induces neighboring cells to transcribe Nodal. We further show that the Nodal inhibitor Lefty, while biochemically capable of long-range diffusion, also acts locally to control the timing of Nodal spread and therefore of mesoderm differentiation during patterning. Our study establishes a paradigm for tissue patterning by an activator-inhibitor pair.
Studying morphogen gradient formation and reception in mammalian development is challenging. Here, the authors show with human gastruloids that Nodal activity in live cells spreads via a relay mechanism with timing that is locally controlled by Lefty, which dictates mesoderm differentiation timing.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 13/95
/ 14/19
/ 14/35
/ 38/32
/ 38/35
/ 64
/ 96
/ Fluorescent Antibody Technique - methods
/ Gene Expression Regulation, Developmental
/ Genes
/ Human Embryonic Stem Cells - cytology
/ Human Embryonic Stem Cells - metabolism
/ Humanities and Social Sciences
/ Humans
/ In Situ Hybridization, Fluorescence - methods
/ Left-Right Determination Factors - genetics
/ Left-Right Determination Factors - metabolism
/ Ligands
/ Mammals
/ Mesoderm
/ Microscopy, Confocal - methods
/ Microscopy, Fluorescence - methods
/ Proteins
/ Relay
/ Science
