Inducible Genetic Lineage Tracing of Cortical Hem Derived Cajal-Retzius Cells Reveals Novel Properties

Xiaochun Gu,Ying Zhang,Samuel J Pleasure,Chunjie Zhao,Yiquan Wei,Xiaojing Wu,Bin Liu,Yan Yan,Marc Tjwa

doi:10.1371/journal.pone.0028653

Xiaochun Gu, Ying Zhang + Show 7 more

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https://doi.org/10.1371/journal.pone.0028653

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Abstract

During cortical development, Cajal-Retzius (CR) cells are among the earliest-born subclasses of neurons. These enigmatic neurons play an important role in cortical development through their expression of the extracellular protein, reelin. CR cells arise from discrete sources within the telencephalon, including the pallial-subpallial border and the medial (cortical hem) regions of the pallium. Combined evidence suggests that CR cells derived from distinct origins may have different distributions and functions. By tracing CR cells derived from the cortical hem using the inducible Cre transgenic mouse tool, Frizzled 10-CreER™, we examined the specific properties of hem-derived CR cells during cortical development. Our results show that the progenitor zone for later production of CR cells from the hem can be specifically marked as early as embryonic day 6.5 (E6.5), a pre-neural period. Moreover, using our Cre line, we found that some hem-derived CR cells migrated out along the fimbrial radial glial scaffold, which was also derived from the cortical hem, and preferentially settled in the hippocampal marginal zone, which indicated specific roles for hem-derived CR cells in hippocampal development.

Highlights

Cajal-Retzius (CR) cells are among the earliest-born neurons in the developing cerebral cortex
When cells were labeled by the yellow fluorescent protein (YFP) reporter, they were distinguished by the expression of reelin and P73, which were detected by double immunostaining (Fig. 1E–J) and indicated that the hem-derived cells were CR cells from the progenitors that expressed Fzd10 in the cortical hem
Using our transgenic mouse line, we found that the CR cells originating from the cortical hem tangentially migrated to the cortical and hippocampal MZ in an overall posterior-anterior direction (Fig. 4D, H), which differed from the CR cells derived from the pallial-subpallial boundary (PSB) [3]

Summary

Introduction

Cajal-Retzius (CR) cells are among the earliest-born neurons in the developing cerebral cortex. They are found in the marginal zone, the most superficial layer of the cerebral cortex, and play many pivotal roles in cortical development [1,2]. CR cells derived from Dbx1-positive progenitors in the PSB migrate to the dorsolateral and piriform cortex, but CR cells from the septum largely migrate to the rostral-medial and piriform cortices [3]. The ablation of Dbx progenitors with diphtheria toxin fragment A(DTA) starting at embryonic day 11 (E11.0) results in the loss of CR cells in the rostral-medial and dorsolateral pallium, suggesting that CR cells from the PSB have specific functions in early regionalization of the cerebral cortical neuroepithelium [3]

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