Cell lineage-guided mass spectrometry reveals increased energy metabolism and reactive oxygen species in the vertebrate organizer

Molecular understanding of the vertebrate Organizer, a tissue center critical for inductive signaling during gastrulation, has so far been mostly limited to transcripts and a few proteins, the latter due to limitations in detection and sensitivity. The Spemann-Mangold Organizer (SMO) in the South Af...

Full description

Saved in:

Bibliographic Details
Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 121; no. 6; p. e2311625121
Main Authors:	Baxi, Aparna B, Li, Jie, Quach, Vi M, Pade, Leena R, Moody, Sally A, Nemes, Peter
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 06-02-2024
Subjects:	Animals Biological Sciences Body Patterning - genetics Cell Lineage Central nervous system Developmental biology Embryos Energy Metabolism Gastrulation Gene Expression Regulation, Developmental Hydrogen peroxide Intermediates Mass spectrometry Mass spectroscopy Mesoderm Metabolism Metabolites Metabolomics Organizers, Embryonic - physiology Oxidative phosphorylation Oxidative stress Oxygen enrichment Pattern formation Patterning Phosphorylation Physical Sciences Proteins Proteomics Reactive oxygen species Reactive Oxygen Species - metabolism Regulatory proteins Scientific imaging Transcription Factors - metabolism Vertebrates Xenopus laevis - metabolism Xenopus Proteins - metabolism Xenopus mass spectrometry Spemann–Mangold Organizer proteomics metabolomics
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Molecular understanding of the vertebrate Organizer, a tissue center critical for inductive signaling during gastrulation, has so far been mostly limited to transcripts and a few proteins, the latter due to limitations in detection and sensitivity. The Spemann-Mangold Organizer (SMO) in the South African Clawed Frog ( ), a popular model of development, has long been known to be the origin of signals that pattern the mesoderm and central nervous system. Molecular screens of the SMO have identified several genes responsible for the ability of the SMO to establish the body axis. Nonetheless, a comprehensive study of proteins and metabolites produced specifically in the SMO and their functional roles has been lacking. Here, we pioneer a deep discovery proteomic and targeted metabolomic screen of the SMO in comparison to the remainder of the embryo using high-resolution mass spectrometry (HRMS). Quantification of ~4,600 proteins and a panel of targeted metabolites documented differential expression for 460 proteins and multiple intermediates of energy metabolism in the SMO. Upregulation of oxidative phosphorylation and redox regulatory proteins gave rise to elevated oxidative stress and an accumulation of reactive oxygen species in the SMO. Imaging experiments corroborated these findings, discovering enrichment of hydrogen peroxide in the SMO. Chemical perturbation of the redox gradient perturbed mesoderm involution during early gastrulation. HRMS expands the bioanalytical toolbox of cell and developmental biology, providing previously unavailable information on molecular classes to challenge and refine our classical understanding of the Organizer and its function during early patterning of the embryo.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by Carole LaBonne, Northwestern University, Evanston, IL; received July 13, 2023; accepted December 12, 2023 by Editorial Board Member Amy C. Rosenzweig
ISSN:	0027-8424 1091-6490 1091-6490
DOI:	10.1073/pnas.2311625121