A novel TaulacZ allele reveals a requirement for Pitx2 in formation of the mammillothalamic tract

Genesis. 2012 Jan;50(1):67-73. doi: 10.1002/dvg.20793. Epub 2012 Jan 6.

Abstract

The hypothalamic mammillary region is critical for spatial memory and vestibular processing. Pitx2 encodes a paired-like transcription factor that is highly expressed in the developing mammillary region and is required for subthalamic nucleus formation. Here we analyzed a loss of function Pitx2-TaulacZ knock-in allele to study the effects of Pitx2 deficiency on neuronal projections in the embryonic mammillary region. Pitx2-expressing neurons contribute axons to principal mammillary, mammillotegmental and mammillotectal tracts. Embryos with Pitx2 deficiency exhibit axonal fibers in the principal mammillary tract that are improperly bundled and disorganized, yet project caudally toward the tectum and tegmentum. Embryos with Nestin-Cre mediated conditional Pitx2 deficiency exhibit truncated mammillothalamic tracts (mtt) that fail to elongate, and reduced Pax6-positive cells at the branching point of the principal mammillary and mtt. These data suggest that Pitx2 mediates cell-autonomous and nonautonomous guidance cues necessary for mammillary collaterals destined to project to the anterior thalamus.

Publication types

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

MeSH terms

  • Alleles*
  • Animals
  • Axons / metabolism
  • Female
  • Fluorescent Antibody Technique / methods
  • Genotype
  • Hypothalamus / metabolism
  • Integrases / metabolism
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / metabolism
  • Male
  • Mammillary Bodies / embryology*
  • Mammillary Bodies / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Fluorescence / methods
  • Nerve Tissue / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nestin
  • Neurons / metabolism
  • Tegmentum Mesencephali / embryology
  • Tegmentum Mesencephali / metabolism
  • Thalamus / embryology
  • Thalamus / metabolism

Substances

  • Intermediate Filament Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Cre recombinase
  • Integrases