Organ Regeneration Based on Developmental Biology

5

SVZ: the primate (especially human) cortex is characterized by a highly expanded

SVZ, which is subdivided into inner and outer SVZ (ISVZ and OSVZ) (Smart et al.

2002 ). Recent studies have shown that a novel type of neurogenic progenitor exists

in the human OSVZ at midgestation, which is distinct from apical progenitors and

intermediate progenitors (Fietz et al. 2010 ; Hansen et al. 2010 ). These progenitors,

termed outer radial glia (oRG) (or OSVZ progenitors), show similar marker expres-

sion to apical progenitors (Pax6+, Sox2+, Tbr2−) but a distinct morphology: oRG

cells have a basal process extending to the pial surface and lack an apical process

unlike apical progenitors (Fietz et al. 2010 ; Hansen et al. 2010 ) (Fig. 1.2). oRG cells

undergo multiple rounds of self-renewal and generate neurons indirectly through

their daughter cells, which also have an increased capacity for transit amplification.

oRG cells are present in the mouse fetal brain, but the population is very small com-

pared to the human fetal brain (Shitamukai et al. 2011 ; Wang et al. 2011 ). Therefore,

oRG cells are thought to contribute to the species-specific increased number and

diversity of human cortical neurons (Lui et al. 2011 ).

neuroepithelial
cells

MZ: Cajal-Retzius cells

CP

SP

IZ

SVZ :

VZ : apical progenitors (= radial glia)

(Pax6+/Sox2+)

future

cortical layers

II/III

IV

V

VI

early born

late born

“inside-out”

pattern

intermediate progenitors (Tbr2+)

pia

lumen

outer radial glias (Pax6+/Sox2+)

cortical lamination

at the early second trimester

Fig. 1.2 Development of fetal cortical neuroepithelium. During corticogenesis, the neuroepithe-

lial cells convert into neurogenic apical progenitors. The progenitors generate cortical neurons

either directly or through transit progenitors (intermediate progenitors). Outer radial glia is a newly

discovered type of neurogenic progenitor that exists abundantly in human fetal cortex. The new-

born neurons migrate and settle in the appropriate laminae in an inside-out pattern. The cortical

plate finally forms six neuronal layers. LGE lateral ganglionic eminence; MGE medial ganglionic

eminence; MZ marginal zone; CP cortical plate; SP subplate; IZ intermediate zone; SVZ subven-

tricular zone, VZ ventricular zone

1 Telencephalic Tissue Formation in 3D Stem Cell Culture