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A novel role for Pax6 in the segmental organization of the hindbrain

Research output: Contribution to journalArticle

  • Galya Kayam
  • Ayelet Kohl
  • Zohar Magen
  • Yuval Peretz
  • Karen Weisinger
  • Avi Bar
  • Orna Novikov
  • Claude Brodski
  • Dalit Sela-Donenfeld

Related Edinburgh Organisations

Original languageEnglish
Pages (from-to)2190-202
Number of pages13
JournalDevelopment
Volume140
Issue number10
DOIs
Publication statusPublished - May 2013

Abstract

Complex patterns and networks of genes coordinate rhombomeric identities, hindbrain segmentation and neuronal differentiation and are responsible for later brainstem functions. Pax6 is a highly conserved transcription factor crucial for neuronal development, yet little is known regarding its early roles during hindbrain segmentation. We show that Pax6 expression is highly dynamic in rhombomeres, suggesting an early function in the hindbrain. Utilization of multiple gain- and loss-of-function approaches in chick and mice revealed that loss of Pax6 disrupts the sharp expression borders of Krox20, Kreisler, Hoxa2, Hoxb1 and EphA and leads to their expansion into adjacent territories, whereas excess Pax6 reduces these expression domains. A mutual negative cross-talk between Pax6 and Krox20 allows these genes to be co-expressed in the hindbrain through regulation of the Krox20-repressor gene Nab1 by Pax6. Rhombomere boundaries are also distorted upon Pax6 manipulations, suggesting a mechanism by which Pax6 acts to set hindbrain segmentation. Finally, FGF signaling acts upstream of the Pax6-Krox20 network to regulate Pax6 segmental expression. This study unravels a novel role for Pax6 in the segmental organization of the early hindbrain and provides new evidence for its significance in regional organization along the central nervous system.

    Research areas

  • Animals, Brain, Brain Mapping, Cell Proliferation, Chick Embryo, Cycloheximide, Early Growth Response Protein 2, Electroporation, Eye Proteins, Gene Expression Regulation, Developmental, Genotype, Green Fluorescent Proteins, Homeodomain Proteins, In Situ Hybridization, MafB Transcription Factor, Mice, Paired Box Transcription Factors, Repressor Proteins, Rhombencephalon, Signal Transduction, Time Factors

ID: 13158012