Neural Subtype Poster 840x552mm05:Layout 1 11/10/2010 13:21 Page 1

Glutamatergic cortical neurogenesis
Progenitor domains of developing forebrain

Temporal development of the neocortex

By Benedikt Berningerand Abcam

Layered structure of developed neocortex

Medialpallium

Astrocyte

Young neuron

Neurogenic basal progenitor

Radial glial cell

Oligodendrocytic basal progenitor

Deep & Upper
layer neuron

Stellate neuron

Ventral lateral ganglioniceminence
Medial ganglionic eminence
The dorsal part of the mouse (E 12.5) forebrain(purple area) is the germinative zone for variouskinds of excitatory neurons of the neocortex (usingthe transmitter glutamate) as well as corticalastrocytes and some oligodendrocytes.
In contrast, most, if not all, cortical interneurons(inhibitory neurons using the transmitter GABA) arise

from the medial ganglionic eminence (MGE) of theventral forebrain (grey area) from whence theymigrate tangentially into the neocortex.
Mutual negative loops of transcription factors define
the boundary between the domains of the dorsal andventral forebrain.

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TIME

Ventricularzone

Dorsal lateral
ganglionic eminence

Neuroepithelium

Ventral pallium

Subventricularzone

Marginal zone

LateralpalliumIIII

EMBRYONIC
Neuroepithelial
celll Notch1
n AP2γn Emx1n Emx2n Hes1n Hes5n ki67n NICDn P-H3n Pax6n Tailless

IIIIIYoung neurons DCX
s Lis1s Trim32
n Neurog2

At an early stage, the developing neocortex consists of a single
layered epithelium, called the neuroepithelium. Neuroepithelial
cells divide generating both new epithelial cells and some earlyneurons (Cajal-Retzius cells) which settle in the marginal zone.
Subsequently, neuroepithelial cells transform into radial glia, aprocess which involves upregulation of glial markers such asRadial glial ErbB2 l GLASTl Notch1 l Notch3
s aPKC s BLBP
s Pals1 s Par3s Par6n AP2γn Emx1 n Emx2n Sox2n Hes1n Hes5n ki67
n P-H3n Neurog1n Neurog2 n Pax6
n Tailless

Basalprogenitor
n Brn1n Brn2n Cux1n Cux2n Tbr2n Neurog1
n Neurog2
n phNeurog2

Young neurons βIII tubulins DCXn Math2n NeuroD
n phNeurog2
n Tbr1

Deep layer
neuronn Ctip2
n Fezf2
n NeuNn Sox5n Tbr1

Radial glian AP2γBasal progenitor
n Cux1n Cux2n NeuroD4
n Neurog2
n Tbr2BLBP and GLAST. These radial glial cells self-renew as stem
cells and generate the next wave of neurons. By virtue of theirlong radial process towards the pial surface, radial glia also
serve as a scaffold for the migration of neurons towards thedeveloping cortical plate.
At later stages, radial glia begin to give rise to new types ofRadial glia
(generating astroglia)
n Ring1B
n Olig2

progenitors, called basal progenitors, thereby creating a newgerminative zone, the so-called subventricular zone. These, inturn, divide generating either neurons or a next generation ofbasal progenitors.
Neurons continue to migrate towards the cortical plate where
they settle in an inside-out fashion, i.e. later born neurons passl PlxnD1, n Bhlhb5,n Brn1, n Brn2,n Cux1, n Cux2,n Lhx2, n Mef2c,n Tle1, n Tle3l PlxnD1, n Bhlhb5,n Brn1, n Brn2,n Cux1, n Cux2,n Lhx2, n Lmo3,n Mef2c, n Tle1,n Tle3
T other partsToo the cortexofIVV

n Bhlhb5, n Brn1,n Cux1, n Cux2,n Lhx2, n Mef2c

Vl PlxnD1, l Sema3e,n Bhlhb5, n Brn1,n Brn2, n Clim1,n Ctip2, n Er81,n Fezf2, n FoxO1,n Lmo4, n Otx1,n Satb2, n Sox5,n Tle4

VIl Sema3e, n Ctip2,n Fezf2, n Foxp2,n Lmo3, n Otx1,n Sox5, n Tle4
To other partsof the brain andspinal cord

BIRTH

Early born
young neurons βIII tubulin
s DCX
s Reelin

l Reelin, n Lhx5

To other parts
Too the cortex
ofIntermediate
zone

Cortical hemI

Upper layer
neuronn Cux1n Cux2n Satb2n NeuN
Astrocytel GLASTl GLT1s GFAPs Glutaminesynthetases S100βKeyl : Membrane

The developed neocortex consists of six layers(enumerated by Roman numbers). Layer I harbors few
cells and most neurons are located between layers II-VI.
Generally, neurons of the deeper layers have been
generated earlier than those of the upper layers.
They differ in morphology, connectivity and theiraxonal projection from each other.
Selective expression of transcription factors isresponsible for this specification. Some transcription
factors are expressed only during specific phases,
while others persist. This allows for the identificationof the distinct subtypes of glutamatergic neurons
based on their transcription factor expression.
Not depicted are a variety of GABAergic interneurons(originating from the ventral telencephalon),
responsible for local inhibition.

s : Intracellularn : Nuclear

earlier born neurons, thus creating the distinct cortical layers.
At late corticogenesis (around birth), radial glia lose theirneurogenic potential and either transform directly into astrocytes
or give rise to astrocyte progenitors.
Some of the radial glia also generate progenitors foroligodendrocytes or transform into ependymal cells (not depicted).

References:
Guillemot F. Cellular and molecular control of neurogenesis in the mammalian telencephalon. Curr Opin Cell Biol. 2005, 17(6):639-47.
Heinrich C, Blum R, Gascón S, Masserdotti G, Tripathi P, Sánchez R, Tiedt S, Schroeder T, Götz M, Berninger B. Directing
astroglia from the cerebral cortex into subtype specific functional neurons PLoS Biol. 2010, 8(5):e1000373.
Kriegstein A. and Alvarez-Buylla A. The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci. 2009,
32:149-84.
Molyneaux BJ, Arlotta P, Menezes JR, Macklis JD. Neuronal subtype specification in the cerebral cortex. Nat Rev Neurosci.
2007, 8:427-37.
Pinto L and Götz M. Radial glial cell heterogeneity-the source of diverse progeny in the CNS. Prog Neurobiol. 2007, 83:2-23.

Dr. Benedikt Berninger is a researcher at the Institute of Physiology, LMU München, Germany. He works on the specification ofneural stem cells into specific neuron subtypes as well as the re-specification of parenchymal glia into neurons (reprogramming).

148-10/10-PS

Neuroepithelial cell

Corticalplate

Dorsalpallium

MarginalzoneKey