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Reelin-expressing Cajal-Retzius (CR) cells are among the earliest generated cells in the mammalian cerebral cortex and are believed to be crucial for both the development and the evolution of a laminated pattern in the pallial wall of the telencephalon. LIM-homeodomain (LIM-hd) transcription factors are expressed during brain development in a highly restricted and combinatorial manner, and they specify regional and cellular identity. We have investigated the expression of the LIM-hd members  Lhx1/Lhx2/Lhx5/Lhx6/Lhx9  in the reelin-expressing cells, the pallium, and the regions of origin of CR cells including the cortical hem of 3 amniote species: the mouse, the chick, and the macaque monkey. We found major differences in the combinatorial LIM-hd expression in the marginal zone as well as in the hem. 1)  Lhx5  is a “preferential LIM-hd” for CR cells in mammals but not expressed by these cells in chicks. 2)  Lhx2  is expressed in the hem of the chick, whereas it is excluded from this region in mouse. 3) Whereas mouse CR cells express  Lhx5/Lhx1 , their monkey counterparts express 4 of these factors:  Lhx1/Lhx2/Lhx5/Lhx9 . We discuss our findings in evolutionary terms for the specification of the midline hem and CR cell type and the emergence of the cortical lamination pattern.

Differential Expression of LIM-Homeodomain Factors in Cajal-Retzius Cells of Primates, Rodents, and Birds