Compensatory Actions of Ldb Adaptor Proteins During Corticospinal Motor Neuron Differentiation

<span class="paragraphSection"><div class="boxTitle">Abstract</div>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. <span style="font-style:italic;">Ldb1</span>-deficient brains display severe defects in proliferation and changes in regionalization, phenotypes resembling those of <span style="font-style:italic;">Lhx</span> mutants. <span style="font-style:italic;">Ldb2</span>-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 <span style="font-style:italic;">Ldb2</span> single-mutant mice reveals a compensatory role of <span style="font-style:italic;">Ldb1</span> for <span style="font-style:italic;">Ldb2</span> during corticospinal motor neuron (CSMN) differentiation. Animals lacking both <span style="font-style:italic;">Ldb1</span> and <span style="font-style:italic;">Ldb2</span> uncover the requirement for <span style="font-style:italic;">Ldb2</span> during CSMN differentiation, manifested as incomplete CSMN differentiation, and ultimately leading to a failure of the corticospinal tract.</span>

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