Neural Subtype Poster 840x552mm05:Layout 1 11/10/2010 13:21 Page 1
Key
Dorsal pallium
Medial pallium
Cortical hem
Neuroepithelial cell
Young neuron
Radial glial cell
Deep & Upper layer neuron
Astrocyte
Neurogenic basal progenitor
Oligodendrocytic basal progenitor
Stellate neuron
II I
I II I l Reelin, n Lhx5 l PlxnD1, n Bhlhb5, n Brn1, n Brn2, n Cux1, n Cux2, n Lhx2, n Mef2c, n Tle1, n Tle3
To other parts l PlxnD1, n Bhlhb5, n Brn1, n Brn2, n Cux1, n Cux2, n Lhx2, n Lmo3, n Mef2c, n Tle1, n Tle3
To other parts
Lateral pallium
Ventral pallium
Dorsal lateral ganglionic eminence
Ventral lateral ganglionic eminence
Medial ganglionic eminence
The dorsal part of the mouse (E 12.5) forebrain
(purple area) is the germinative zone for various kinds of excitatory neurons of the neocortex (using the transmitter glutamate) as well as cortical astrocytes 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 the ventral forebrain (grey area) from whence they migrate tangentially into the neocortex.
Mutual negative loops of transcription factors define the boundary between the domains of the dorsal and ventral forebrain.
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TIME EMBRYONIC BIRTH
Neuroepithelial cell l Notch1 n AP2 γ n Emx1 n Emx2 n Hes1 n Hes5 n ki67 n NICD n P-H3 n Pax6 n Tailless
Early born young neuron s β III tubulin s DCX s Reelin
Young neuron s DCX s Lis1 s Trim32 n Neurog2
Radial glia l ErbB2 l GLAST l Notch1 l Notch3 s aPKC s BLBP s Pals1 s Par3 s Par6 n AP2 γ n Emx1 n Emx2 n Sox2 n Hes1 n Hes5 n ki67 n P-H3 n Neurog1 n Neurog2 n Pax6 n Tailless
Basal progenitor n Brn1 n Brn2 n Cux1 n Cux2 n Tbr2 n Neurog1 n Neurog2 n phNeurog2
Young neuron s β III tubulin s DCX n Math2 n NeuroD n phNeurog2 n Tbr1
Radial glia n AP2 γ
Deep layer neuron n Ctip2 n Fezf2 n NeuN n Sox5 n Tbr1
Basal progenitor n Cux1 n Cux2 n NeuroD4 n Neurog2 n Tbr2
Radial glia
(generating astroglia) n Ring1B n Olig2
Upper layer neuron n Cux1 n Cux2 n Satb2 n NeuN
Astrocyte l GLAST l GLT1 s GFAP s Glutamine
synthetase s S100 β
Key l : Membrane s : Intracellular n : Nuclear
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 early neurons (Cajal-Retzius cells) which settle in the marginal zone.
Subsequently, neuroepithelial cells transform into radial glia, a process which involves upregulation of glial markers such as
BLBP and GLAST. These radial glial cells self-renew as stem cells and generate the next wave of neurons. By virtue of their long radial process towards the pial surface, radial glia also serve as a scaffold for the migration of neurons towards the developing cortical plate.
At later stages, radial glia begin to give rise to new types of progenitors, called basal progenitors, thereby creating a new germinative zone, the so-called subventricular zone. These, in turn, divide generating either neurons or a next generation of basal progenitors.
Neurons continue to migrate towards the cortical plate where they settle in an inside-out fashion, i.e. later born neurons pass earlier born neurons, thus creating the distinct cortical layers.
At late corticogenesis (around birth), radial glia lose their neurogenic potential and either transform directly into astrocytes or give rise to astrocyte progenitors.
Some of the radial glia also generate progenitors for oligodendrocytes or transform into ependymal cells (not depicted).
n Bhlhb5, n Brn1, n Cux1, n Cux2, n Lhx2, n Mef2c l 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 l Sema3e, n Ctip2, n Fezf2, n Foxp2, n Lmo3, n Otx1, n Sox5, n Tle4
To other parts of the brain and spinal cord
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 their axonal projection from each other.
Selective expression of transcription factors is responsible for this specification. Some transcription factors are expressed only during specific phases, while others persist. This allows for the identification of 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.
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 of neural stem cells into specific neuron subtypes as well as the re-specification of parenchymal glia into neurons (reprogramming).