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

Abstract

Background

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

Methods

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

Results

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.

Conclusions

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.

References

  1. 1.

    Wilkins-Haug, L. & Freedman, W. Progression of exencephaly to anencephaly in the human fetus–an ultrasound perspective. Prenat. Diagn. 11, 227–233 (1991).

    CAS  Article  Google Scholar 

  2. 2.

    Stumpf The infant with anencephaly. N. Engl. J. Med. 322, 669–674 (1990).

    Article  Google Scholar 

  3. 3.

    Ashwal, S. et al. Anencephaly: clinical determination of brain death and neuropathologic studies. Pediatr. Neurol. 6, 233–239 (1990).

    CAS  Article  Google Scholar 

  4. 4.

    Anand, M. K., Verma, M. & Lakhani, C. Development of brain and spinal cord in anencephaly. FASEB J. 29, 2 (2015).

    Google Scholar 

  5. 5.

    Rakic, P. Specification of cerebral cortical areas. Science 241, 170–176 (1988).

    CAS  Article  Google Scholar 

  6. 6.

    Cunningham, C. L., Martínez-Cerdeño, V. & Noctor, S. C. Microglia regulate the number of neural precursor cells in the developing cerebral cortex. J. Neurosci. 33, 4216–4233 (2013).

    CAS  Article  Google Scholar 

  7. 7.

    Barger, N. et al. Microglia: an intrinsic component of the proliferative zones in the fetal rhesus monkey (Macaca mulatta) cerebral cortex. Cereb. Cortex 29, 2782–2796 (2019).

  8. 8.

    Noctor, S. C. et al. Periventricular microglial cells interact with dividing precursor cells in the nonhuman primate and rodent prenatal cerebral cortex. J. Comp. Neurol. 527, 1598–1609 (2018).

    Article  Google Scholar 

  9. 9.

    Noctor, S. C., Martínez-Cerdeño, V., Ivic, L. & Kriegstein, A. R. Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat. Neurosci. 7, 136–144 (2004).

    CAS  Article  Google Scholar 

  10. 10.

    Noctor, S. C., Martínez-Cerdeño, V. & Kriegstein, A. R. Distinct behaviors of neural stem and progenitor cells underlie cortical neurogenesis. J. Comp. Neurol. 508, 28–44 (2008).

    Article  Google Scholar 

  11. 11.

    Martínez-Cerdeño, V. et al. Comparative analysis of the subventricular zone in rat, ferret and macaque: evidence for an outer subventricular zone in rodents. PLoS ONE 7, e30178 (2012).

    Article  Google Scholar 

  12. 12.

    Copp, A. J. & Greene, N. D. E. Neural tube defects–disorders of neurulation and related embryonic processes. Wiley Interdiscip. Rev. Dev. Biol. 2, 213–227 (2013).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

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). https://doi.org/10.1038/s41390-019-0687-y

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