TY - JOUR T1 - A Hedgehog-FGF signaling axis patterns anterior mesoderm during gastrulation JF - bioRxiv DO - 10.1101/736322 SP - 736322 AU - Alexander Guzzetta AU - Mervenaz Koska AU - Megan Rowton AU - Junghun Kweon AU - Hunter Hidalgo AU - Heather Eckhart AU - Rebecca Back AU - Stephanie Lozano AU - Anne M. Moon AU - Anindita Basu AU - Michael Bressan AU - Sebastian Pott AU - Ivan P. Moskowitz Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/08/16/736322.abstract N2 - The application of single cell technologies to early development holds promise for resolving complex developmental phenotypes. Here we define a novel role for Hedgehog (Hh) signaling for the formation of anterior mesoderm lineages during gastrulation. Single-cell transcriptome analysis of Hh-deficient mesoderm revealed selective deficits in anterior mesoderm populations that later translate to physical defects to anterior embryonic structures including the first pharyngeal arch, heart, and anterior somites. We found that Hh-dependent anterior mesoderm defects were cell non-autonomous to Hh-signal reception. Transcriptional profiling of Hh-deficient mesoderm during gastrulation revealed disruptions to both transcriptional patterning of the mesoderm and a key FGF signaling pathway for mesoderm migration. FGF4 protein application was able to restore cellular migration during gastrulation that was decreased by Hh pathway antagonism. These findings implicate that primitive streak-mediated regulation of anterior mesoderm patterning is controlled by a multicomponent signaling hierarchy activated by Hh signaling and executed by FGF signal transduction.SIGNIFICANCE STATEMENT How signaling events during gastrulation pattern the mesoderm is a fascinating developmental process. Although Hedgehog signaling has been implicated in early mesoderm development, its mechanistic role has not been described. We applied single cell sequencing to describe mesodermal defects in Hedgehog pathway mutants—revealing selective defects in anterior mesoderm populations. Transcriptional profiling of gastrulating Hedgehog mutants indicated that several pathways essential for primitive streak function, including FGF, required Hh signaling. Blocking Hedgehog signaling abrogated cell migration during gastrulation, which could be mitigated by addition of FGF4 ligand. This work uncovers a novel Hedgehog to FGF signaling event and describes a unique mechanism by which signals from the node impact to anterior mesoderm formation through the modulation of primitive streak function. ER -