Neuroembryology II_UniTsNeurosciAY1415_06a

UniTs-Neurobiology Degree
Neuroembryology II course, AY 2014-2015
A.Mallamaci, SISSA
lesson 6:
(1) origin and migration of layer I neurons
(2) origin and migration of cortical interneurons
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 origin and migration of layer I neurons
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are cortical neurons all generated by precursors located within
the dorsal telencephalic wall?
(1) Bayer & Altmann (1991) classically assume that common precursors located in the dorsal
telencephalic wall give rise to the entire neocortical neuronal complement.
(2) more recently, it has been demonstrated that more and more laminar neuronal subpopulations derive from dedicated ancestors located outside the dorsal telencephalon. In
rodents, these subpopulations are:
- Interneurons (located throughout the cortex, generated by MGE and CGE)
- Cajal-Retzius cells (located in layer I, generated by CH, VP and septum)
[further subpopulations originating outside the pallium have been also described in rodents and
humans]
(3) conversely, genetic labelling of glutamatergic neurons via an Emx1-driven cre transgene
(Rubenstein, 2004) firmly proved that the almost totality of cortical glutamatergic neurons are
generated by precursors expressing Emx1, so located within the dorsal telencephalic wall.
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neurons form exogenous sources: mouse layer I Cajal-Retzius cells
generation of Cajal-Retzius by specialized regions of the telencephalon was originally
proposed by G. Mayer on the basis of the accurate time course analysis of murine and human
embryonic samples (1999, 2002, 2004).
occurrence of these phenomena in the mouse was formally proven by the groups of Y.Tanabe
(2004) and A.Pierani (2005).
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Cajal-Retzius cells from the
cortical hem
Tanabe and collaborators co-electroporated a tracer
lacZ-expressor plasmid and a CR-marker plasmid
(expressing EGFP under the control of a promoter
which specifically fires in CR-cells) into the E11.5
telencephalon, at different locations.
After a few days, they studied the resulting
distribution of the two markers and could prove that:
(1) CR-cells are specifically generated by the
cortical hem as well as - to a minor extent - by the
antero-medial telencephalic pole;
(2) therefrom, they tangentially diffuse to far
locations.
Accurate time course analysis of the
system suggested that hemgenerated CR-cells spread all over
the telencephalon, playing a major
role in the coverage of dorsal,
caudal-medial regions of it.
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Cajal-Retzius cells from
ventral pallium and septum
A.Pierani and collaborators found that the
homeogene Dbx1 is specifically expressed
by ventral pallium and septum
in order to follow the fate of the
descendants of these Dbx1-expressing
cells, they alternatively knocked into the
Dbx1 locus two different cds:
(1) nsl-lacZ, whose protein product,
more stable than Dbx1, allows mid-term
chasing of these progenies
(2) cre, whose protein product may
allow irreversible functional activation of
an nls-lacZ cds born by another transgene,
constitutively transcribed but basally silent
as preceded by a floxed STOP cassette
extensive co-localisation of beta-gal and
Reln occurring in telencephala of the
resulting mice mutants allowed to prove
that CR-cells covering paleocortex and
lateral neocortex derive to large extent
from the two Dbx1-expressing districts
described above.
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apparent functional redundance of the different sources of CR-cells_I
NB. Dbx1 promoter restricts the manipulation to ventral pallium-derivatives;
Nes promoter restricts cre expression to apical precursors
the group of A. Pierani (2005) genetically ablated ventral pallium and septum, by
intersectional DT-A mutagenesis, but could not get a reeler phenotype.
this was reasonably due to partial working of the ablation system as well as to the replacement of non-hem derived CR-cells by hem-derived ones, massively occurring by E14.5
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apparent functional redundance of the different sources of CR-cells_II
the group of E.Grove (2005) genetically ablated the cortical
hem, again by intersectional DT-A mutagenesis, but was not
able to get a reeler phenotype.
in this case, non-hem derived CR-cells hardly replaced hemderived ones, because of their modest spreading to dorsomedial territories occurring in Wnt3axneoxdta/+Emx1IREScre/+
mutants.
moreover, the secondary source of Reln which appears in
presumptive layers V-IV starting from E14.5-E15.5, was not
impaired in these mutants.
as a consequence of that, no reeler phenotype was observed
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neurons form exogenous sources: human layer I neurons
Bystron et al (2006) re-analyzed the genesis of layer I in the human cortex and found a
scenario considerably much more complex than in rodents. She described four neuronal
subtypes, two generated by local precursors (“locally generated” and Cajal-Retzius, ???),
two generated elsewhere (predecessor and olfactory epithelium derivatives). The biological
meaning of all that is obscure.
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