Characterization of progenitor cells during the development of the ventral telencephalon of the mouse

During development of the mammalian telencephalon stem cells and
more lineage restricted progenitor cells give rise to all cell
types which later are contributing to this fascinatingly
orchestrated organ. Initially, at the stage of neuroepithelial
cells, these stem cells increase their pool by symmetric
proliferative divisions and later, when matured to radial glia (RG)
cells they give rise to neurons either directly, or indirectly via
intermediate progenitors. At later stages of development, radial
glia generate glial progenitor cells or differentiate to glial
cells directly. How stem cells orchestrate this sequel of tissue
genesis has been unraveled by pioneer studies focusing on stem
cells of the murine cerebral neocortex. However, the ways how one
of the biggest brain regions of the murine brain, the ventral
telencephalon which later forms the basal ganglia, facilitates this
process, have been largely unknown. Over the past years, increasing
interest has been put forward in understanding how the human cortex
and its dramatically expanded surface with gyri and sulci is build
up on a cellular level during embryonic development. Studies both
on embryonic human and primate brains revealed that an expanded
germinal zone, the outer subventricular zone (OSVZ), seeded with a
heterogeneous population of progenitor cells which are rare in
lissencepahlic brains, is responsible to form this enormously
elevated brain region. However, both human and primate material is
rare and genetically modified models are not available. To
investigate the cellular mechanisms taking place in an expanded
mammalian brain region in the mouse would be of great interest
technically and from an evolutionary perspective. Therefore,
live-imaging studies of individual progenitor cells in embryonic
brainslices which have been labeled in the lateral ganglionic
eminence (LGE) by in-utero electroporation were carried out to
reveal lineages emanating from single RG cells. The development of
the ventral telencephalon precedes that of the dorsal
telencephalon, the cerebral neocortex, and already at early stages
prominent bulges begin t form into the ventricular lumen. One
characteristic of ventral forebrain development is the early
appearance of a non-apically dividing cell population away from the
ventricle, which outnumbers from stages of midneurogenesis on
apically dividing cells. Amongst these non-apically dividing cells
a proportion divides in the ventricular zone, a region that in the
neocortex is largely devoid of mitotic cells. These subapically
dividing cells were termed according to their location subapical
progenitors (SAP). The characterization of these SAPs both by
immunohistochemistry and live imaging revealed a morphologically
heterogeneous population, with cells bearing processes towards
apical, basal or both directions in addition to cells without
processes resembling the morphology of basal progenitors, during
mitosis. Indeed, bipolar cells amongst these SAPs were
characterized as a new type of radial glia, which does not reach
the ventricular surface for mitosis but divides in the VZ and
generates a basally migrating bRG. By this SAPs contribute to the
seeding of the LGE SVZ with a cell type that is characteristic for
enlarged SVZ, like the OSVZ in gyrified brains and fundamental for
the formation of gyri and sulci. The longterm observation of RG
lineages in the LGE uncovered the potential to generate large
progeny at midneurogenesis. RG give rise to daughter cells which
divide once more in the ventricular zone and generate cells with
further proliferative potential, thereby amplifying the cellular
output. This amplification of progenitor cells goes along with a
shortening in cell cycle length, a feature observed also in the
expanded germinal zones of gyrified cortices. In conclusion the
developing murine LGE turns out to be a suitable model to study the
cellular mechanisms of an expanded brain region.