EphB receptor tyrosine kinases control morphological development of the ventral midbrain

Amy L. Altick, Christopher Dravis, Tracey Bowdler, Mark Henkemeyer, Grant S. Mastick

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

EphB receptor tyrosine kinases and ephrin-B ligands regulate several types of cell-cell interactions during brain development, generally by modulating the cytoskeleton. EphB/ephrinB genes are expressed in the developing neural tube of early mouse embryos with distinct overlapping expression in the ventral midbrain. To test EphB function in midbrain development, mouse embryos compound homozygous for mutations in the EphB2 and EphB3 receptor genes were examined for early brain phenotypes. These mutants displayed a morphological defect in the ventral midbrain, specifically an expanded ventral midline evident by embryonic day E9.5-10.5, which formed an abnormal protrusion into the cephalic flexure. The affected area was comprised of cells that normally express EphB2 and ephrin-B3. A truncated EphB2 receptor caused a more severe phenotype than a null mutation, implying a dominant negative effect through interference with EphB forward (intracellular) signaling. In mutant embryos, the overall number, size, and identity of the ventral midbrain cells were unaltered. Therefore, the defect in ventral midline morphology in the EphB2;EphB3 compound mutant embryos appears to be caused by cellular changes that thin the tissue, forcing a protrusion of the ventral midline into the cephalic space. Our data suggests a role for EphB signaling in morphological organization of specific regions of the developing neural tube.

Original languageEnglish (US)
Pages (from-to)501-512
Number of pages12
JournalMechanisms of Development
Volume122
Issue number4
DOIs
StatePublished - Apr 2005

Fingerprint

Eph Family Receptors
Mesencephalon
Protein-Tyrosine Kinases
EphB2 Receptors
Neural Tube
Embryonic Structures
EphB3 Receptor
Ephrin-B3
Head
Ephrins
Phenotype
Mutation
Brain
Cytoskeleton
Cell Communication
Genes
Embryonic Development
Ligands

Keywords

  • Development
  • Eph
  • EphB2
  • EphB3
  • Ephrin
  • Ephrin-B3
  • Midbrain
  • Morphology
  • Neural tube
  • Neuroepithelium

ASJC Scopus subject areas

  • Developmental Biology
  • Developmental Neuroscience

Cite this

EphB receptor tyrosine kinases control morphological development of the ventral midbrain. / Altick, Amy L.; Dravis, Christopher; Bowdler, Tracey; Henkemeyer, Mark; Mastick, Grant S.

In: Mechanisms of Development, Vol. 122, No. 4, 04.2005, p. 501-512.

Research output: Contribution to journalArticle

Altick, Amy L. ; Dravis, Christopher ; Bowdler, Tracey ; Henkemeyer, Mark ; Mastick, Grant S. / EphB receptor tyrosine kinases control morphological development of the ventral midbrain. In: Mechanisms of Development. 2005 ; Vol. 122, No. 4. pp. 501-512.
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