LIM homeodomain transcription factors are critical regulators of early 
development in multiple systems but have yet to be examined for a role in 
circuit formation. The LIM homeobox gene Lhx2 is expressed in cortical 
progenitors during development and also in the superficial layers of the 
neocortex in maturity. However, analysis of Lhx2 function at later stages of 
cortical development has been hampered by severe phenotypes associated with 
early loss of function. We identified a particular Cre-recombinase line that 
acts in the cortical primordium after its specification is complete, permitting 
an analysis of Lhx2 function in neocortical lamination, regionalization, and 
circuit formation by selective elimination of Lhx2 in the dorsal telencephalon. 
We report a profound disruption of cortical neuroanatomical and molecular 
features upon loss of Lhx2 in the cortex from embryonic day 11.5. A unique 
feature of cortical circuitry, the somatosensory barrels, is undetectable, and 
molecular patterning of cortical regions appears disrupted. Surprisingly, 
thalamocortical afferents innervate the mutant cortex with apparently normal 
regional specificity. Electrophysiological recordings reveal a loss of responses 
evoked by stimulation of individual whiskers, but responses to simultaneous 
stimulation of multiple whiskers were present, suggesting that thalamic 
afferents are unable to organize the neurocircuitry for barrel formation because 
of a cortex-specific requirement of Lhx2. We report that Lhx2 is required for 
the expression of transcription factor paired box gene 6, axon guidance molecule 
Ephrin A5, and the receptor NMDA receptor 1. These genes may mediate Lhx2 
function in the formation of specialized neurocircuitry necessary for 
neocortical function.