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Molecular dissection of segment formation in the developing hindbrain.

Charlotte Labalette1, Michel Adam Wassef2, Carole Desmarquet-Trin Dinh1

  • 1Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, CNRS UMR 8197, Paris F-75005, France.

Development (Cambridge, England)
|December 18, 2014
PubMed
Summary

Understanding hindbrain segmentation requires knowing how gene expression patterns form. This study reveals how krox20 gene regulation integrates multiple signals to precisely define rhombomere 3 boundaries during embryogenesis.

Keywords:
Egr2FgfHoxKrox20NlzRhombomereSegmentationTranscriptional enhancerZebrafish

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Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • Positional information during embryogenesis is crucial for tissue specification.
  • The genetic pathways for hindbrain segmentation are partially understood.
  • The precise mechanisms integrating signals to define specific segments remain unclear.

Purpose of the Study:

  • To investigate the molecular mechanisms of rhombomere 3 (r3) formation.
  • To dissect the transcriptional regulation of the krox20 gene in hindbrain segmentation.
  • To understand how different signaling pathways are integrated to specify discrete tissue territories.

Main Methods:

  • Analysis of krox20 transcriptional regulation.
  • Identification of input pathways including Hox paralogous 1 (PG1) factors and Fgf signaling.
  • Investigation of cis-acting elements and gene regulatory networks.

Main Results:

  • Hox PG1 factors directly activate and indirectly repress krox20 expression.
  • Fgf signaling modulates krox20 activity magnitude.
  • Two cis-acting elements and a krox20 positive-feedback loop orchestrate r3 boundary formation.

Conclusions:

  • Positional information from diverse patterning mechanisms is integrated via a gene regulatory network.
  • A krox20 positive-feedback loop refines the initial transcriptional response to establish precise segment boundaries.
  • This study provides a comprehensive view of territory delimitation in hindbrain development.