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Although many genes that specify neocortical projection neuron subtypes have been identified, the downstream effectors that control differentiation of those subtypes remain largely unknown. Here, we demonstrate that the LIM domain-binding proteins Ldb1 and Ldb2 exhibit dynamic and inversely correlated expression patterns during cerebral cortical development.  Ldb1 -deficient brains display severe defects in proliferation and changes in regionalization, phenotypes resembling those of  Lhx  mutants.  Ldb2 -deficient brains, on the other hand, exhibit striking phenotypes affecting layer 5 pyramidal neurons: Immature neurons have an impaired capacity to segregate into mature callosal and subcerebral projection neurons. The analysis of  Ldb2  single-mutant mice reveals a compensatory role of  Ldb1  for  Ldb2  during corticospinal motor neuron (CSMN) differentiation. Animals lacking both  Ldb1  and  Ldb2  uncover the requirement for  Ldb2  during CSMN differentiation, manifested as incomplete CSMN differentiation, and ultimately leading to a failure of the corticospinal tract.

Compensatory Actions of Ldb Adaptor Proteins During Corticospinal Motor Neuron Differentiation