The mouse mutation reeler causes increased adhesion within a subpopulation of early postmitotic cortical neurons

Abstract

Early postmitotic cortical neurons are mostly corticofugal projection neurons that take up positions in deep cortical laminae. Later postmitotic neurons are preferentially localized to superficial cortical laminae. In reeler mutant mice it appears that cortical laminar positions with respect to birthdate are reversed (Caviness, 1982). In a reanalysis of reeler lamination we found that early postmitotic cortical neurons labeled by embryonic day (E) 11-13 injections of a birthdate marker, or by early postnatal day (PND) 2 retrograde labeling through their output projections, appear to take up positions both in the superficial and deep cortex. Neurons born on E11 and E12 are more likely to be situated superficially in the reeler cortex and neurons born on E13 are more likely to be situated in the deep reeler cortex. Many corticofugal projection neurons in the deep (but not superficial) reeler cortex either die or retract their axons before PND 21. We hypothesize that the earliest postmitotic (E11-E12) of the early postmitotic reeler cortical neurons are overly adhesive and act as a barrier to later postmitotic migrating neurons. In vitro cortical aggregation cultures confirmed that early postmitotic (E12) reeler neurons are more adhesive than early postmitotic (E12) wild-type neurons or late postmitotic (E16) reeler or wild-type cortical neurons. We suggest that the moderate wild-type preferential adhesion of early postmitotic cortical neurons to each other helps deep and superficially fated lineages to form cortical laminae.