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  • Review Article
  • Published:

Parsing the prosencephalon

Key Points

  • This review summarizes what has been discovered so far about the extrinsic and intrinsic programmes that participate in the patterning of the telencephalon.

  • The early patterning of anterior and posterior neural tissues is mediated by signals from the node; in addition, the anterior visceral endoderm seems to be required for head induction and maintenance in mammals.

  • Nieuwkoop proposed that nascent neural tissue adopts an anterior identity by default, and that posterior nervous tissue is generated subsequently through a process called 'transformation'. Studies in fish and frogs have implicated Wnt, retinoids and fibroblast growth factor (FGF) as posteriorizing factors.

  • The cells at the junction between the anterior neural and non-neural ectoderm have an important role in promoting telencephalic development within the forebrain territory. The specification of telencephalic identity seems to require the inhibition of posteriorizing signals, such as Wnt.

  • Sonic hedgehog (Shh) signalling is crucial for dorsoventral (DV) patterning at all levels of the nervous system. In the telencephalon, Shh acts through the inhibition of Gli3 repressor activity. However, Shh seems to be dispensable for DV patterning in this region, provided that Gli3 function is also abolished, implying that other signals act in parallel with Shh. These signals include bone morphogenetic proteins, Wnts, retinoids and FGFs.

  • In response to Shh and other extrinsic signals, cells express specific transcription factors, which activate intrinsic cellular programmes that cause progenitors to adopt specific cell fates. These transcription factors include homeodomain proteins and basic helix–loop–helix factors.

  • Until relatively recently, the different regions of the forebrain were thought to develop as independent compartments. However, it has become clear that extensive mixing of cells occurs, perhaps because different progenitor zones generate specific subsets of neural cell types, which subsequently become widely distributed throughout the telencephalon.

  • Now that a broad outline of telencephalic development is crystallizing, it seems likely that further resolution of the underlying mechanisms will rely on direct examination of this region, rather than on extrapolation from other regions of the nervous system.

Abstract

The forebrain, or prosencephalon, consists of the diencephalon and the telencephalon. The diencephalon is the conduit for ascending sensory information, whereas the telencephalon is the highest-order processor of neural function, and is consequently the most complex region of the nervous system. In this review, we discuss how fate restrictions, starting from the induction of neural character, result in the sequential specification of anterior neural tissue, forebrain and telencephalon, and finally dorsoventral patterning. Rather than relying on novel signalling pathways, the complexity of the mature brain seems to result from the unique ordering of signals used widely during development.

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Figure 1: Signals and tissues involved in inducing anterior neural character.
Figure 2: Progressive specification of the telencephalon.
Figure 3: Model of genetic interactions between Shh and Gli3 in patterning the mouse telencephalon.
Figure 4: Homeodomain and bHLH genetic interactions in telencephalic development.

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Acknowledgements

We thank all members of the Fishell lab for their critical reading of this review. We are also grateful to S. Wilson for his many helpful suggestions and for clarification of our worst misstatements. Our work is supported by the National Institutes of Health (NIH), a March of Dimes basic research grant and a Children's Brain Tumor Foundation grant to G.F.; and by postdoctoral grants from l'Association pour la Recherche Contre le Cancer to M.R, from the American Cancer Society to N.G and from the NIH to J.C. and R.M. Finally, including all the important findings on the telencephalon in a single review is an impossible task. Where possible, we have cited reviews, rather than primary sources, to be as inclusive as possible. We hope that the many authors of important papers on the subject that we have failed to mention will forgive us for our oversights.

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Correspondence to Gord Fishell.

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DATABASES

Entrez

cerberus

dickkopf

Tlc

Wnt

FlyBase

achaete-scute complex

atonal

cubitus interruptus

eyeless

H2.0

Hedgehog

ind

msh

Smoothened

vnd

LocusLink

Axin

Bf1

Bmp2b

BMP4

BMP7

chordin

Dbx1

Dbx2

Dlx1

Dlx2

Emx1

FGF3

FGF8

follistatin

Frzb

Gli1

Gli2

Gli3

Gsh1

Gsh2

Hesx1

Ihh

Lim1

Mash1

Ngn1

Ngn2

Nkx2.1

Nkx2.2

Nkx6.1

Nodal

noggin

Notch

Olig1

Olig2

Otx2

Pax6

Shh

Smo

TGF-β

FURTHER INFORMATION

Encyclopedia of Life Sciences

bone morphogenetic proteins and their receptors

hedgehog signalling

mammalian embryo: Wnt signalling

neural development: bHLH genes

neural subtype identity regulation

signal transduction pathways in development: Wnts and their receptors

vertebrate central nervous system: pattern formation

The Fishell Lab

Glossary

HOMEODOMAIN

A 60-amino-acid DNA-binding domain that comprises three α-helices and is found in many transcription factors.

BASIC HELIX–LOOP–HELIX

(bHLH). A structural motif present in many transcription factors that is characterized by two α-helices separated by a loop. The helices mediate dimerization, and the adjacent basic region is required for DNA binding.

NODE

A major organizing centre in primitive-streak-stage embryos that regulates pattern formation. It is known as Hensen's node in chick and the Spemann organizer in frog.

EPIBLAST

The outer layer of a blastula, which gives rise to the ectoderm after gastrulation.

PRECHORDAL PLATE

A tissue derived from the node, which lies at the rostral tip of the notochord.

MESENDODERM

Embryonic tissue that gives rise both to mesoderm and endoderm.

PRESOMITIC MESODERM

Precursor unsegmented mesoderm, which generates somites on segmentation.

SUBPALLIAL

Belonging to the base of the telencephalon. The subpallium consists primarily of the basal ganglia, including the striatum, globus pallidus, and parts of the septum and amygdala.

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Rallu, M., Corbin, J. & Fishell, G. Parsing the prosencephalon. Nat Rev Neurosci 3, 943–951 (2002). https://doi.org/10.1038/nrn989

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