Emx1 and Emx2 cooperate to regulate cortical size, lamination, neuronal differentiation, development of cortical efferents, and thalamocortical pathfinding

Kathie M. Bishop, Sonia Garel, Yasushi Nakagawa, John L R Rubenstein, Dennis D M O'Leary

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

The homeobox transcription factors Emx1 and Emx2 are expressed in overlapping patterns that include cortical progenitors in the dorsal telencephalic neuroepithelium. We have addressed cooperation of Emx1 and Emx2 in cortical development by comparing phenotypes in Emx1; Emx2 double mutant mice with wild-type and Emx1 and Emx2 single mutants. Emx double mutant cortex is greatly reduced compared with wild types and Emx single mutants; the hippocampus and dentate gyrus are absent, and growth and lamination of the olfactory bulbs are defective. Cell proliferation and death are relatively normal early in cortical neurogenesis, suggesting that hypoplasia of the double mutant cortex is primarily due to earlier patterning defects. Expression of cortical markers persists in the reduced double mutant neocortex, but the laminar patterns exhibited are less sharp than normal, consistent with deficient cytoarchitecture, probably due in part to reduced numbers of preplate and Reelin-positive Cajal-Retzius neurons. Subplate neurons also exhibit abnormal differentiation in double mutants. Cortical efferent axons fail to exit the double mutant cortex, and TCAs pass through the striatum and approach the cortex but do not enter it. This TCA pathfinding defect appears to be non-cell autonomous and supports the hypothesis that cortical efferents are required scaffolds to guide TCAs into cortex. In double mutants, some TCAs fail to turn into ventral telencephalon and take an aberrant ventral trajectory; this pathfinding defect correlates with an Emx2 expression domain in ventral telencephalon. The more severe phenotypes in Emx double mutants suggest that Emx1 and Emx2 cooperate to regulate multiple features of cortical development.

Original languageEnglish (US)
Pages (from-to)345-360
Number of pages16
JournalJournal of Comparative Neurology
Volume457
Issue number4
DOIs
StatePublished - Jan 27 2003

Keywords

  • Axon guidance
  • Corticogenesis
  • Corticothalamic axons
  • Dentate gyrus
  • Handshake hypothesis
  • Hippocampus
  • Marginal zone
  • Neocortex
  • Olfactory bulb
  • Preplate
  • Reelin
  • Subplate
  • Telencephalon
  • Thalamocortical axon pathfinding
  • Transcription factors

Fingerprint Dive into the research topics of 'Emx1 and Emx2 cooperate to regulate cortical size, lamination, neuronal differentiation, development of cortical efferents, and thalamocortical pathfinding'. Together they form a unique fingerprint.

Cite this