Abstract
Cajal–Retzius (CR) neurons play a critical role in cortical neuronal migration, but their exact fate after the completion of neocortical lamination remains a mystery. Histological evidence has been unable to unequivocally determine whether these cells die or undergo a phenotypic transformation to become resident interneurons of Layer 1 in the adult neocortex. To determine their ultimate fate, we performed chronic in vivo two-photon imaging of identified CR neurons during postnatal development in mice that express the green fluorescent protein (GFP) under the control of the early B-cell factor 2 (Ebf2) promoter. We find that, after birth, virtually all CR neurons in mouse neocortex express Ebf2. Although postnatal CR neurons undergo dramatic morphological transformations, they do not migrate to deeper layers. Instead, their gradual disappearance from the cortex is due to apoptotic death during the second postnatal week. A small fraction of CR neurons present at birth survive into adulthood. We conclude that, in addition to orchestrating cortical layering, a subset of CR neurons must play other roles beyond the third postnatal week.
Highlights
More than a century after their discovery (Ramón y Cajal, 1890; Retzius, 1893), Cajal–Retzius (CR) neurons remain mysterious cells surrounded by controversy (Soriano and Del Rio, 2005)
Recent work has identified early B-cell factor 2 (Ebf2) as a marker of CR neurons originating from the ventral pallium, but perhaps not those from the cortical hem (Yamazaki et al, 2004; Hanashima et al, 2007)
We used Ebf2-green fluorescent protein (GFP) transgenic mice (GENSAT2) because the available online data suggested that they express GFP in cells of L1 in postnatal cortex, and that those cells exhibit the typical morphology of CR neurons, making this line ideally suited for chronic in vivo imaging
Summary
More than a century after their discovery (Ramón y Cajal, 1890; Retzius, 1893), Cajal–Retzius (CR) neurons remain mysterious cells surrounded by controversy (Soriano and Del Rio, 2005). Recent evidence suggests that the vast majority of CR neurons are most likely generated at E10–12 in three locations: the cortical hem (Takiguchi-Hayashi et al, 2004; Garcia-Moreno et al, 2007), the septum and the ventral pallium (Bielle et al, 2005). They subsequently migrate tangentially to cover the whole cortical mantle, but CR neurons from different sources may eventually populate distinct cortical regions (Bielle et al, 2005).
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