An evolutionarily conserved Lhx2-Ldb1 interaction regulates the acquisition of hippocampal cell fate and regional identity

Development. 2020 Oct 19;147(20):dev187856. doi: 10.1242/dev.187856.

Abstract

The protein co-factor Ldb1 regulates cell fate specification by interacting with LIM-homeodomain (LIM-HD) proteins in a tetrameric complex consisting of an LDB:LDB dimer that bridges two LIM-HD molecules, a mechanism first demonstrated in the Drosophila wing disc. Here, we demonstrate conservation of this interaction in the regulation of mammalian hippocampal development, which is profoundly defective upon loss of either Lhx2 or Ldb1 Electroporation of a chimeric construct that encodes the Lhx2-HD and Ldb1-DD (dimerization domain) in a single transcript cell-autonomously rescues a comprehensive range of hippocampal deficits in the mouse Ldb1 mutant, including the acquisition of field-specific molecular identity and the regulation of the neuron-glia cell fate switch. This demonstrates that the LHX:LDB complex is an evolutionarily conserved molecular regulatory device that controls complex aspects of regional cell identity in the developing brain.

Keywords: Hippocampus; Ldb1; Lhx2; Tetramer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning
  • Cell Lineage*
  • Conserved Sequence*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Evolution, Molecular*
  • Hippocampus / cytology*
  • LIM Domain Proteins / genetics*
  • LIM Domain Proteins / metabolism
  • LIM-Homeodomain Proteins / genetics*
  • LIM-Homeodomain Proteins / metabolism
  • Mice
  • Mutation / genetics
  • Neurogenesis
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Protein Binding
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • LIM Domain Proteins
  • LIM-Homeodomain Proteins
  • Ldb1 protein, mouse
  • Lhx2 protein, mouse
  • Transcription Factors