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The fundamental building blocks of cortical development are established in human exencephaly



The presence and status of progenitor/stem cells in excencephalic brain have not been previously examined.


Brain sections of excencephalic 17-week fetus were stained for specific stem and mature cell markers.


The ventricles were open, the developing cerebral cortex was thin in the radial dimension, and the ventricular surface was undulated. There was a decreased ratio of subventricular/ventricular zone radial glia precursor cells (RGCs; PAX6+ and HOPX+ cells), a decreased number of intermediate progenitor cells (IPCs; TBR2+), a decreased number of neurons (MAP2+), and an increased number of astrocytes (S100b+), compared to the control. MAP2+ neurons, S100b+ astrocytes, and OLIG2+ oligodendrocytes were present within the subventricular zone.


This indicates that the underlying condition did not initially preclude radial glial cells from undergoing asymmetric divisions that produce IPCs but halted the developmental progression. RGC and IPC presence in the developing cerebral cortex demonstrates that the fundamental building blocks of cortical formation had been established and that a normal sequence of developmental steps had been initiated in this case of exencephaly. These data expand our understanding of exencephaly etiology and highlight the status of cortical progenitor cells that may be linked to the disorder.

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Fig. 1: Exencephaly brain anatomy.
Fig. 2: Progenitor and neural cell identity in the cerebral cortex of exencephaly and age-matched control feti.

Data availability

The data sets generated during and/or analyzed during the current study are available from the corresponding author upon request.


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We thank the family who donated the case, Sherry Middleton, and the Shiners Hospitals who facilitated the process of donation. This work was supported by R01 MH094681 (NIH/NIMH), R011NS107131 (NIH/NINDS), NSF CAMPOS Award, and Shriners Hospitals for Children of Northern California.

Author contributions

C.F. performed the experiments and co-wrote the manuscript, G.V. co-performed experiments, S.C.N. co-wrote the manuscript, and V.M.-C. designed the experiments and wrote the manuscript.

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Correspondence to Verónica Martínez-Cerdeño.

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The authors declare no competing interests.

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Falcone, C., Vakilzadeh, G., Noctor, S.C. et al. The fundamental building blocks of cortical development are established in human exencephaly. Pediatr Res 87, 868–871 (2020).

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