Lhx2, an evolutionarily conserved, multifunctional regulator of forebrain development

Brain Res. 2019 Feb 15;1705:1-14. doi: 10.1016/j.brainres.2018.02.046. Epub 2018 Mar 6.


A hundred years after Lhx2 ortholog apterous was identified as a critical regulator of wing development in Drosophila, LIM-HD gene family members have proved to be versatile and powerful components of the molecular machinery that executes the blueprint of embryogenesis across vertebrate and invertebrate species. Here, we focus on the spatio-temporally varied functions of LIM-homeodomain transcription factor LHX2 in the developing mouse forebrain. Right from its earliest known role in telencephalic and eye field patterning, to the control of the neuron-glia cell fate switch, and the regulation of axon pathfinding and dendritic arborization in late embryonic stages, LHX2 has been identified as a fundamental, temporally dynamic, always necessary, and often sufficient factor in a range of critical developmental phenomena. While Lhx2 mutant phenotypes have been characterized in detail in multiple brain structures, only recently have we advanced in our understanding of the molecular mechanisms by which this factor acts. Common themes emerge from how this multifunctional molecule controls a range of developmental steps in distinct forebrain structures. Examining these shared features, and noting unique aspects of LHX2 function is likely to inform our understanding of how a single factor can bring about a diversity of effects and play central and critical roles across systems and stages. The parallels in LHX2 and APTEROUS functions, and the protein complexes they participate in, offer insights into evolutionary strategies that conserve tool kits and deploy them to play new, yet familiar roles in species separated by hundreds of millions of years.

Keywords: Hippocampus; Hypothalamus; Neocortex; Optic; Telencephalon; Thalamus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Evolution
  • Cell Differentiation
  • Gene Expression Regulation, Developmental / genetics
  • Homeodomain Proteins / genetics
  • LIM-Homeodomain Proteins / genetics
  • LIM-Homeodomain Proteins / metabolism*
  • LIM-Homeodomain Proteins / physiology*
  • Mice
  • Neurogenesis / physiology
  • Neuroglia / metabolism
  • Neurons / metabolism
  • Prosencephalon / embryology*
  • Prosencephalon / metabolism
  • Spatio-Temporal Analysis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription Factors / physiology*


  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Lhx2 protein, mouse
  • Transcription Factors