Abstract
The hindbrain roof plate and choroid plexus are essential organizing centers for inducing dorsal neuron fates and sustaining neuron function. To map the formation of these structures, we developed a broadly applicable, high resolution, recombinase-based method for mapping the fate of cells originating from coordinates defined by intersecting combinations of expressed genes. Using this method, we show that distinct regions of hindbrain roof plate originate from discrete subdomains of rhombencephalic neuroectoderm expressing Wnt1; that choroid plexus, a secretory epithelium important for patterning later-formed hindbrain structures and maintaining neuron function1, derives from the same embryonic primordium as the hindbrain roof plate; and that, unlike the floor plate2,3, these dorsal organizing centers develop in a patterned, segmental manner, built from lineage-restricted compartments. Our data suggest that the roof plate and choroid plexus may be formed of functional units that are capable of differentially organizing the generation of distinct neuronal cell types at different axial levels.
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Acknowledgements
We thank S. Schneider-Maunoury for the Egr2::cre mouse strain; A. McMahon for plasmids pWEXP2 and pSP72MT34; T. Lufkin for the rhombomere 2–specific enhancer of Hoxa2; S. Thor for sequences encoding eGFPF; G. Martin for the pACTB::cre plasmid; J. Flanagan for plasmids encoding Eph receptors and their ligands; C. Tabin for a plasmid encoding cadherin-6; C. Tabin, C. Branda and A. Farago for critical reading of this manuscript; and S. Blackshaw for useful discussions. Work in the laboratories of S.M.D. and P.S. was supported by grants from the US National Institutes of Health. R.A. was supported by a Wills Foundation postdoctoral fellowship award and is currently supported by Taplin Funds for Discovery.
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Awatramani, R., Soriano, P., Rodriguez, C. et al. Cryptic boundaries in roof plate and choroid plexus identified by intersectional gene activation. Nat Genet 35, 70–75 (2003). https://doi.org/10.1038/ng1228
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DOI: https://doi.org/10.1038/ng1228
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