Lhx2 regulates a cortex-specific mechanism for barrel formation

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• LIM homeodomain transcription factors regulate early development.
• Lhx2 is expressed in developing and mature neocortex.
• Early Lhx2 loss-of-function causes severe phenotypes, hindering later developmental analysis.

Purpose of the Study:

• To investigate the role of Lhx2 in neocortical circuit formation, lamination, and regionalization.
• To analyze Lhx2 function in later cortical development using a specific Cre-recombinase line.

Main Methods:

• Utilized a Cre-recombinase line for selective Lhx2 elimination in the dorsal telencephalon post-specification.
• Examined neuroanatomical and molecular features of the developing neocortex.
• Performed electrophysiological recordings to assess cortical responses.

Main Results:

• Loss of Lhx2 from embryonic day 11.5 profoundly disrupted cortical neuroanatomy and molecular patterning.
• Somatosensory barrels were undetectable, and regional molecular patterns were altered.
• Thalamocortical afferents maintained regional specificity, but Lhx2-deficient cortex failed to organize sensory circuitry, indicated by altered whisker response patterns.

Conclusions:

• Lhx2 is critically required for neocortical circuit formation, specifically for organizing the somatosensory barrel cortex.
• Lhx2 regulates the expression of key genes including Pax6, Ephrin A5, and NMDAR1, which likely mediate its function in specialized neurocircuitry.
• These findings highlight a cortex-specific role for Lhx2 in establishing functional neural circuits essential for neocortical function.