Molecular diversity of early-born subplate neurons.

Subplate cells in the mouse are generally defined as cells located in the subplate layer between the white matter and layer 6a. They are some of the earliest born and maturing cells of the cerebral cortex. The postnatal subplate layer in mouse contains neurons with expression of the presynaptic protein complexin 3 (Cplx3), connective tissue growth factor (CTGF), the orphan nuclear receptor Nr4a2 (Nurr1), and the G-protein-coupled lysophosphatidic acid receptor 1 (Lpar1/Edg2). All 4 of these molecular markers show layer 6b-restricted expression at young postnatal ages, with CTGF expression being the most widespread in the young postnatal subplate. However, all 4 markers overlap in their expression pattern to varying degrees. Here we demonstrate with bromodeoxyuridine birthdating that cells labeled with any 1 of these molecular subplate markers are indeed generated at E11.5 or E12.5 in the mouse. Furthermore, we demonstrate a correlation between gene expression and cell birthdates. Lpar1-GFP cells are preferentially generated on E11.5, whereas Cplx3 or Nurr1-positive cells are equally generated during the 2-day peak of subplate neurogenesis (E11.5-E12.5). Our study also demonstrates that early-born subplate neurons labeled by Cplx3, Nurr1, and Lpar1-GFP survive preferentially after the first postnatal week compared with other subplate neurons.