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The genetics of early telencephalon patterning: some assembly required

Key Points

  • The embryonic telencephalon starts off as a simple sheet of neuroepithelial cells. This neuroepithelium becomes patterned into distinct proliferative zones that ultimately generate the different neural cell types that make up the adult cerebral hemispheres.

  • Four broad regions can be defined in the early telencephalic neuroepithelium: a cortical area that generates primarily glutamatergic neurons, a dorso-medial area that induces the hippocampus and produces the choroid plexus, a ventro-medial area that generates subtypes of GABA (γ-aminobutyric acid)-ergic interneurons, and a caudo-lateral area that generates different subtypes of interneurons and inhibitory projection neurons.

  • The development of the ventral areas of the telencephalon is established by the attenuation of dorsalizing signals by sonic hedgehog and the activation of ventral patterning by fibroblast growth factors.

  • Forkhead box G1 interacts with different factors and is required for both dorsal and ventral patterning.

  • Establishment of the pallial–subpallial boundary involves antagonistic interactions between key transcription factors, including NKX2.1, paired box 6, GSH2 and TLX.

  • A dorsal midline organizer helps to establish pallial subdivisions.

Abstract

The immense range of human behaviours is rooted in the complex neural networks of the cerebrum. The creation of these networks depends on the precise integration of specific neuronal subtypes that are born in different regions of the telencephalon. Here, using the mouse as a model system, we review how these proliferative zones are established. Moreover, we discuss how these regions can be traced back in development to the function of a few key genes, including those that encode fibroblast growth factors (FGFs), sonic hedgehog (SHH), bone morphogenetic proteins (BMPs), forkhead box G1 (FOXG1), paired box 6 (PAX6) and LIM homeobox protein 2 (LHX2), that pattern the early telencephalon.

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Figure 1: Key extrinsic and intrinsic cellular factors establish the dorsal and ventral subdivisions of the telencephalon.
Figure 2: The dorsal and ventral telencephalic regions are subdivided into four major domains.
Figure 3: FGF signalling as an organizer for the telencephalon.
Figure 4: Key genetic pathways that interact to form and pattern the early telencephalon.

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Acknowledgements

We would like to apologize to the authors of the many studies that have not been mentioned owing to lack of space. We would like to thank the many members of the Hébert and Fishell laboratories who read and offered suggestions on this Review, especially Drs Rossignol, Machold, Sousa, Demarco and Karayannis. In addition we would like to thank J. Dasen and B. Rudy for their comments on earlier versions of this manuscript. This research was supported by US National Institutes of Health grants to J.H. and G.F., as well as by funding from the Simons Foundation to G.F. and from the McDonnell and Sinsheimer Foundations to J.H.

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Glossary

Neuroepithelium

The embryonic ectoderm that develops into the nervous system.

Neural plate

The neural epithelial cells that form in the early embryo after neuronal induction and give rise to the nervous system.

Anlagen

An embryonic precursor of a more mature tissue.

Morphogen

A secreted factor that can induce two or more different cell fates in a concentration-dependent manner by forming a gradient.

Pallium

The roof of the telencephalon (but not synonymous with the cortex). It contains both cortical structures (for example, the hippocampus and the neocortex) and deep-lying nuclear structures (for example, the claustrum and parts of the amygdala).

Cortical hem

A transient structure located in the dorso-medial area of the embryonic telencephalon, between the hippocampal anlagen and the choroid plexus. The cortical hem acts as a hippocampal organizer.

Mitogen

An agent that induces mitosis, usually resulting in cell division.

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Hébert, J., Fishell, G. The genetics of early telencephalon patterning: some assembly required. Nat Rev Neurosci 9, 678–685 (2008). https://doi.org/10.1038/nrn2463

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