Lecture 10 (5a) - Neural Stem Cells in Vertebrates and Invertebrates Flashcards
In Drosophila neuroblasts segregate from the
neuroectoderm and the neuroblast progeny are passively dispaced towards interior
• stem cells divide symmetrically to make more (self-renewing)
• asymmetrically –> diff cell fates
The postmitotic neurons migrate
out of the ventricular zone and establish the distinct brain layers
Despite the different morphologies, conserved genes
are expressed during neurogenesis in vertebrates
• proneural genes
achaete-scute homologues
atonal family
• neurogenic genes - members of the notch signalling pathway
All cells express
proneural genes
but notch represses
• determine how many stem cells are formed at 1 time
Neurogenin is expressed
in broad stripes in the neural plate of xenopus
• neural plate (outside) folds in and makes neural tube
Notch signalling keeps
neural precursor in the epithelium
• Notch keeps neural stem cells pool - ensures symmetric division
• no Notch –> premature divides asymmetrically –> no stem cells
• only fate of newly born neurons (embryonic lethal)
Notch signalling has an additional function in vertebrates
Notch signalling is necessary for maintaining the neural stem cell pool
Proneural genes have different/additional functions in vertebrates
- proneural genes promote the generation of neurons but also SUPPRESS THE FORMATION OF GLIAL CELLS (astrocytes) in mammals
- proneural genes are required for the DELAMINATION and MIGRATION of neurons
- proneural genes promote CELL CYCLE EXIT
In mammals, proneural genes suppress
astroglial differentiation and
promote neural development
Proneural gene function in vertebrates is required for
delamination and migration
In contrast to Drosophila, proneural genes promote
cell cycle in vertebrates
• Drosophila = no migration
Proneural and neurogenic gene are
conserved in vertebrates and invertebrates
• but these genes have partially different/additional functions
(homologs)
Neurogenesis can be subdivided into 4 processes
- generation of neural stem cells
- establishment o neural precursor identity
- differentiation of neural precursors
- establishment of neuronal networks
2 main processes contribute to the generation of neural diversity (mainly in invertebrates)
- spatial patterning (info from place)
* temporal regulation of formation (timing)
In vertebrates, the identity of a neuron can be influenced
- as it migrates to its final position
* after innervation of its target tissue
Regional identity genes
establish neuroblast diversity in Drosophila
• segment polarity for ant/post identity
• stripes in each segment
• remain expressed in neuroectoderm and later specifically in neuroblasts
• longitudinal overlapping –> grid pattern (dorso/ventral)
• each proneural cluster gets positional identity
The expression profiles of the neuroblasts determine
the identity o their progeny
• motor and interneurons need even-skipped
• PCC and ACC - longitudinal, motor neurons
• PLACE AFFECTS PROGENY
Gray = neuroblasts express
Msh
• no Msh in lateral
(not expressed throughout neurogenesis - only 2 divisions then off)
Msh expressed in
- lateral domain of ventral ectoderm in spider
- continuous lateral domain in the millipede
- temporal and spatial variations in arthropods
The early motor and interneuronal marker eve and islet are expressed in
subsets of NPGs in the spider
Msh regulates
islet expression in the lateral ectoderm
• regional identity genes regulate neuronal sub-type identity similar to Drosophila
- region determines fate
- drosophila gene regulation doesn’t transfer to explain it in other organisms
Evolutionary changes in the regulation of
neuronal sub-type specific genes in arthropods
Msh =
Msx in vertebrates
Temporal identity
The dorso-ventral patterning genes are
conserved in vertebrates
The number of divisions and type of progeny produced is
pre-planned
Temporal identity genes establish
diversity among the progeny of individual neuroblasts
• color = same neuroblast, delaminates
• divide and change to expression of another gene
• later expression –> dies
Temporal identity in Drosophila
all segments at the same time
• growth then segmentation in others
The expression of temporal genes leads to
the formation of distinct neuronal subtypes in neuroblasts 5-6T
• NB 5-6T produces a mixed lineage of 20 cells
• the 4 last born cells are interneurons expressing Apterous (LIM-homeodomain) transcription factor
• the 4 Ap neurons can be further subdivided into 3 different neuronal subtypes
Similar to Drosophila, there is a strong link between
time of formation and neural identity
• neurons are generated first followed by astrocytes and oligodendrocytes
• ventral motorneurons are born first followed by dorsal interneurons
• the ability of the neural stem cells to produce diverse neural cell types becomes restricted over time
–> Notch signalling and additional factors
Neuronal subtype identity genes are expressed in response
to the spatial and temporal identity cues
• LIM proteins regulate subtype specificity in motorneurons
Summary
- in all bilaterians, neural stem cells are generated in a single layered neuroepithelium
- proneural genes specify neural stem cells
- neurogenic genes restrict the number of neural stem cells
- spatial and temporal identity mechanisms establish the identity of individual neural stem cells and their progeny
Euarthropods have a
rope/ladder-like axonal
• 2 longitudinal tracts, 2 transversal to connect
• conserved mechanisms = axonal scaffold
• evolutionary modifications = neuronal network
Euarthropods show different mechanisms of
neural precursor formation
Despite differences in the morphology of neural precursor generation
conserved genes are expressed
• proneural proteins (members of the Achaete-Scute family) endow cells w/ neural potential
• the members of the Notch signalling pathway restrict the activity of the proneural genes to a subset of cells
• Notch signalling restricts number
In insects, proneural genes are expressed in
groups of cells PRONEURAL CLUSTERS
D. melanogaster achaete-scute
–> Notch signalling
–> single-spaced neuroblasts (~30)
• neuroblasts don’t segregate
- in perimeter - in neuroblasts
The achaete-scute homologues of chelicerates and myriapods are
up-regulated in pronerual domains
CsASH, CmASH
–> Notch signalling
–> spaced neural precursor groups (~30 NPGs)
- achaete-scute homologues are up-regulated in neuroblasts
- always arrangement of 7 rows of neuroblasts/precursors
Daphnia magna ASH is exclusively
up-regulated in neuroblasts - proneural clusters are missing Dam ASH Dam asense neuroblasts are not spaced (hemi-neuromere)
The ancestral pattern of euarthropod neurogenesis
neuroblasts • hexapoda • crustacea neural precursor groups • myriapoda • chelicerata single neural precursors • onychophora
Ek ASh is not up-regulated in
spatio-temporal domains in the VNE
• ASH upregulated in segregated neural precursors
• low homogenous ASH in VNE
Onychophoran neurogenesis doesn’t reflect the state of euarthropod neurogenesis
- proneural genes are up-regulated in proneural clusters/domains or even single neuroblasts (crustaceans) in a regular spatio-temporal patern in ventral neuroectoderm of euarthropods
- the onychophoran proneural gene is not spatio-temporally regulated in the ventral neuroectoderm
Conserved pattern of neuroblasts/neural precursors groups in euarhtropods
(insect, crustacean, millipede, spider)
- about 25-35 neuroblasts/NPGs
- neuroblasts/NPGs are arranged in 7 row
- molecular marker gene expression (engrailed)
In contrast to euarthropods, a large number of
neural precursors segregates in an irregular pattern in onychophorans
• 60-100 neural precursors segregate in each hemi-neuromere
• onychophorans - random precursor arrangement
Groups of ectodermal cells are selected in the
ventral neuroectoderm of basal insects
The ancestral state of neural precursor group selection is
maintained in diverse neurogenic regions in insects
• 3 groups of neural precursors invaginate from the stomodeal epithelium and directly differentiate into neurons
• part of the neuroendocrine system of Drosophila derives from neural precursor groups that form in the dorsal midline of the embryonic brain
