Abstract

SummaryGene regulatory networks govern pattern formation and differentiation during embryonic development. Segmentation of somites, precursors of the vertebral column among other tissues, is jointly controlled by temporal signals from the segmentation clock and spatial signals from morphogen gradients. To explore how these temporal and spatial signals are integrated, we combined time-controlled genetic perturbation experiments with computational modeling to reconstruct the core segmentation network in zebrafish. We found that Mesp family transcription factors link the temporal information of the segmentation clock with the spatial action of the fibroblast growth factor signaling gradient to establish rostrocaudal (head to tail) polarity of segmented somites. We further showed that cells gradually commit to patterning by the action of different genes at different spatiotemporal positions. Our study provides a blueprint of the zebrafish segmentation network, which includes evolutionarily conserved genes that are associated with the birth defect congenital scoliosis in humans.

Highlights

  • A challenge in developmental biology is providing a molecular description of the cascade of regulatory steps that result in morphological changes and cell differentiation

  • This study provides a blueprint of the zebrafish segmentation network, incorporating genes with homologs in humans that are associated with congenital scoliosis

  • Transcription of mespaa Is Rapidly Repressed by the Segmentation Clock Owing to the complementary expression of her and mesp family genes, we hypothesized a regulatory interaction between them

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Summary

Introduction

A challenge in developmental biology is providing a molecular description of the cascade of regulatory steps that result in morphological changes and cell differentiation. Vertebrate somite segmentation is an example of a regulatory cascade and provides a system for studying the coordinated expression of multiple genes controlled by interconnected signaling pathways. Errors in this regulatory cascade result in various birth defects, including congenital scoliosis (Pourquie, 2011). Her mRNA period increases from posterior end of the PSM to the anterior end of the PSM. Her mRNA oscillations are synchronized between neighboring cells.

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