Rostral optic tectum acquires caudal characteristics following ectopic engrailed expression

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Engrailed (En) homeobox gene expression forms a rostral-to-caudal gradient in the dorsal mesencephalon.
• This En gradient is the earliest marker for chick optic tectum polarity and correlates with cytoarchitecture and retinotectal projections.
• En gradient correlates with RAGS and ELF-1 expression, key for retinotopic projections by excluding temporal axons.

Purpose of the Study:

• To investigate the function of Engrailed (En) in determining optic tectum polarity.
• To understand the molecular mechanisms underlying En-mediated polarity establishment.

Main Methods:

• Used replication-competent retroviral vector RCAS to misexpress mouse En-1 in the chick tectal primordium.
• Analyzed changes in cytoarchitectonic differentiation and molecular markers (RAGS, ELF-1) in misexpressing embryos.
• Performed in vitro membrane stripe assays to assess axonal repulsion by tectal membranes.

Main Results:

• Misexpression of En in the rostral tectum induced a caudal phenotype, abolishing the normal gradient of differentiation.
• RAGS and ELF-1 molecular markers were strongly expressed in the rostral tectum following En misexpression.
• Cell membranes from En-misexpressing rostral tectum preferentially repelled temporal axons.

Conclusions:

• Results support a role for Engrailed (En) in establishing rostrocaudal polarity in the developing optic tectum.
• Upregulation of RAGS and ELF-1 following En misexpression provides a molecular basis for altered axon guidance.
• Demonstrates how En misexpression can lead to nasal axons forming ectopic connections and temporal axons being excluded from the rostral tectum.