Novel IgCAM, MDGA1, expressed in unique cortical area- and layer-specific patterns and transiently by distinct forebrain populations of Cajal-Retzius neurons

The laminar and area patterning of the mammalian neocortex are two organizing principles that define its functional architecture. Members of the immunoglobulin (1g) superfamily of cell adhesion molecules influence neural development by regulating cell adhesion, migration, and process growth. Here we describe the dynamic expression of the unique Ig-containing cell adhesion molecule, MAM domain-containing glycosylphosphatidylinositol anchor 1 (MDGA1), during forebrain development in mice and compare it with other markers. We show that MDGA1 is a layer-specific marker and an area-specific marker, being expressed in layers 2/3 throughout the neocortex, but within the primary somatosensory area (Sl), MDGAI is also uniquely expressed in layers 4 and 6a. Comparisons with other markers, including cadherins, serotonin, cytochrome oxidase, RORP, and COUP-TF1, reveal unique features of patterned expression of MDGA1 within cortex and S1 barrels. Further, our findings indicate that at earlier stages of development, MDGA1 is expressed by Reelin- and Tbr1-positive Caial-Retzius neurons that originate from multiple sources outside of neocortex and emigrate into it. At even earlier stages, MDGA1 is expressed by the earliest diencephalic and mesencephalic neurons, which appear to migrate from a MDGA1-positive domain of progenitors in the diencephalon and form a "preplate." These findings show that MDGAI is a unique marker for studies of cortical lamination and area patterning and together with recent reports suggest that MDGA1 has critical functions in forebrain/midbrain development.