Linking asymmetric cell division to the terminal differentiation program of postmitotic neurons in C. elegans

Dev Cell. 2009 Apr;16(4):563-75. doi: 10.1016/j.devcel.2009.02.011.

Abstract

How asymmetric divisions are connected to the terminal differentiation program of neuronal subtypes is poorly understood. In C. elegans, two homeodomain transcription factors, TTX-3 (a LHX2/9 ortholog) and CEH-10 (a CHX10 ortholog), directly activate a large battery of terminal differentiation genes in the cholinergic interneuron AIY. We establish here a transcriptional cascade linking asymmetric division to this differentiation program. A transient lineage-specific input formed by the Zic factor REF-2 and the bHLH factor HLH-2 directly activates ttx-3 expression in the AIY mother. During the terminal division of the AIY mother, an asymmetric Wnt/beta-catenin pathway cooperates with TTX-3 to directly restrict ceh-10 expression to only one of the two daughter cells. TTX-3 and CEH-10 automaintain their expression, thereby locking in the differentiation state. Our study establishes how transient lineage and asymmetric division inputs are integrated and suggests that the Wnt/beta-catenin pathway is widely used to control the identity of neuronal lineages.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Differentiation*
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / metabolism
  • Female
  • Interneurons / cytology
  • Interneurons / metabolism
  • Mitosis*
  • Models, Biological
  • Molecular Sequence Data
  • Neurons / cytology*
  • Neurons / metabolism
  • Wnt Proteins / metabolism
  • beta Catenin / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Wnt Proteins
  • beta Catenin