NOTES NEUROSCIENCE
1. Brain development
-Neurodevelopmental disorders (intellectual disability, epilepsy, autism, schizophrenia) are
associated with malformations of the brain. Overlap. No effective treatment.
-Key steps during nervous system development
> Starts soon after gastrulation (E4-5w) and extends into mid-20s.
1.1 Early stages in neural development
> Nervous system is derived from neuroectoderm. Neural plate folds to form the neural tube.
Neural tube extends along the whole-body axis as a hollow cylinder.
> Developing nervous system is organized along two main axes: anterior (head)/ posterior
(tail) and dorsal (back) / ventral (belly). Two-dimensional coordinate system, positional
information used by neural stem cells to differentiate into specific types of neurons.
> Neural tube that forms brain is subdivided into 5 neuromeres along the AP axis:
• Telencephalon: cerebral cortex, basal ganglia, hippocampal formation, amygdala,
olfactory bulb.
• Diencephalon: thalamus, hypothalamus, epithalamus, retina
• Mesencephalon: midbrain (substantia nigra)
• Metencephalon: Pons and cerebellum
• Myencephalon: medulla
• Caudal part of neural tube: spinal cord
,> Forebrain (telencephalon, diencephalon) part forms cerebral cortex
> Midbrain (mesencephalon) gives rise to substantia nigra
> Hindbrain (metencephalon, myencephalon) gives rise to cerebellum.
-Patterning of dorsal/ ventral neural tube
> Regional patterning or regionalization is the process
that divides the neuroectoderm up into areas that will
lay the basis for regional specialization of a structure
in the mature nervous system.
> Positional information provides cells with
information on their location within the
neuroepithelium to differentiate into these specific
cell types.
> Next to sheet of cells there is a specialized group of cells (organizer/ signaling center) which
produces a secreted molecule that acts as a morphogen. Set up a concentration gradient of
morphogen which can be measured by cells which differentiate to different types depending
on their threshold.
> Spemann and Mangold’s experiments on amphibian blastophore showed that cells in the
early embryo that would normally form the surface ectoderm (and eventually the skin) can
be induced to change their fates by an organizer transplanted into their midst. These cells
must, therefore, retain the ability, or competence, to adopt other fates.
Building Brains. Price, Jarman, Mason & Kind, (2017). 2nd edition. John Wiley & Son Ltd
> Neural tube has signaling centers in the roof plate (dorsal), and floor plate (ventral).
Opposing BMP from the dorsal end and SHH from the ventral end drive patterning of the
neural tube
> The developing spinal cord is subdivided in progenitor domains that give rise to specific
classes of neurons.
,> SHH controls formation of ventral interneurons and motor neurons in a concentration
dependent manner. Patterns ventral spinal cord and brain.
• Seen using chick embryos, at different SHH concentrations neural plate tissue
differentiated into different types of neurons.
> SHH controls progenitor domain specific expression of several homeodomain transcription
factors which can confer identity to cells. These can be subdivided into 2 classes:
• Class I (repressed by SHH) in the middle part of the neural tube.
• Class II (induced by SHH) in the most ventral part of the neural tube.
> Transcription factors often have exact expression domain boundaries; they repress each
other’s expression. The combination of factors expressed in a region allows cells to develop
into specific types of neurons.
> Signals received by cells specify their fates by activating intracellular transduction pathways
that regulate their gene expression and hence their molecular constitution and phenotype.
Many signaling pathways are used repeatedly for different purposes throughout
development. Building Brains. Price, Jarman, Mason & Kind, (2017). 2nd edition. John Wiley
& Son Ltd
, -Patterning of anterior/ posterior neural tube
> Specific regions along the anterior/posterior axis control patterning. Often boundaries
between the different parts of the brain.
> The best‐studied example of this is the isthmic organizer, a group of cells formed close to
the future midbrain–hindbrain boundary. This expresses FGF8 and Wnt1, which diffuse locally
to activate a number of genes. It is required to specify the tectum anteriorly and the
cerebellum posteriorly. Building Brains. Price, Jarman, Mason & Kind, (2017). 2nd edition.
John Wiley & Son Ltd
> The ZLI patterns the diencephalon locally by producing Sonic hedgehog (SHH). Activates the
transcription factor genes Dlx2 on the anterior side and Gbx2 on the posterior side. This
differential response to SHH leads to the formation of the prethalamus and thalamus,
respectively. The basis of this difference depends on the pre‐existing expression of the gene
Irx3 posterior to the ZLI. Building Brains. Price, Jarman, Mason & Kind, (2017). 2nd edition.
John Wiley & Son Ltd
1.2 Brain size control
> Cerebral cortex confers humans with unique cognitive capabilities. Required for all higher
cognitive functions, malformations underlie several neurodevelopmental disorders such as
microcephaly/ macrocephaly, autism spectrum disorders and schizophrenia.
> Size and functional complexity is thought to be behind higher cognitive function of humans
compared to other mammalian species.
-Factors affecting brain size:
> Rate of apoptosis/ programmed cell death
• During development nervous system produces excess of neurons, neurons must make
proper contact with their target cells and if they fail, they are eliminated.
1. Brain development
-Neurodevelopmental disorders (intellectual disability, epilepsy, autism, schizophrenia) are
associated with malformations of the brain. Overlap. No effective treatment.
-Key steps during nervous system development
> Starts soon after gastrulation (E4-5w) and extends into mid-20s.
1.1 Early stages in neural development
> Nervous system is derived from neuroectoderm. Neural plate folds to form the neural tube.
Neural tube extends along the whole-body axis as a hollow cylinder.
> Developing nervous system is organized along two main axes: anterior (head)/ posterior
(tail) and dorsal (back) / ventral (belly). Two-dimensional coordinate system, positional
information used by neural stem cells to differentiate into specific types of neurons.
> Neural tube that forms brain is subdivided into 5 neuromeres along the AP axis:
• Telencephalon: cerebral cortex, basal ganglia, hippocampal formation, amygdala,
olfactory bulb.
• Diencephalon: thalamus, hypothalamus, epithalamus, retina
• Mesencephalon: midbrain (substantia nigra)
• Metencephalon: Pons and cerebellum
• Myencephalon: medulla
• Caudal part of neural tube: spinal cord
,> Forebrain (telencephalon, diencephalon) part forms cerebral cortex
> Midbrain (mesencephalon) gives rise to substantia nigra
> Hindbrain (metencephalon, myencephalon) gives rise to cerebellum.
-Patterning of dorsal/ ventral neural tube
> Regional patterning or regionalization is the process
that divides the neuroectoderm up into areas that will
lay the basis for regional specialization of a structure
in the mature nervous system.
> Positional information provides cells with
information on their location within the
neuroepithelium to differentiate into these specific
cell types.
> Next to sheet of cells there is a specialized group of cells (organizer/ signaling center) which
produces a secreted molecule that acts as a morphogen. Set up a concentration gradient of
morphogen which can be measured by cells which differentiate to different types depending
on their threshold.
> Spemann and Mangold’s experiments on amphibian blastophore showed that cells in the
early embryo that would normally form the surface ectoderm (and eventually the skin) can
be induced to change their fates by an organizer transplanted into their midst. These cells
must, therefore, retain the ability, or competence, to adopt other fates.
Building Brains. Price, Jarman, Mason & Kind, (2017). 2nd edition. John Wiley & Son Ltd
> Neural tube has signaling centers in the roof plate (dorsal), and floor plate (ventral).
Opposing BMP from the dorsal end and SHH from the ventral end drive patterning of the
neural tube
> The developing spinal cord is subdivided in progenitor domains that give rise to specific
classes of neurons.
,> SHH controls formation of ventral interneurons and motor neurons in a concentration
dependent manner. Patterns ventral spinal cord and brain.
• Seen using chick embryos, at different SHH concentrations neural plate tissue
differentiated into different types of neurons.
> SHH controls progenitor domain specific expression of several homeodomain transcription
factors which can confer identity to cells. These can be subdivided into 2 classes:
• Class I (repressed by SHH) in the middle part of the neural tube.
• Class II (induced by SHH) in the most ventral part of the neural tube.
> Transcription factors often have exact expression domain boundaries; they repress each
other’s expression. The combination of factors expressed in a region allows cells to develop
into specific types of neurons.
> Signals received by cells specify their fates by activating intracellular transduction pathways
that regulate their gene expression and hence their molecular constitution and phenotype.
Many signaling pathways are used repeatedly for different purposes throughout
development. Building Brains. Price, Jarman, Mason & Kind, (2017). 2nd edition. John Wiley
& Son Ltd
, -Patterning of anterior/ posterior neural tube
> Specific regions along the anterior/posterior axis control patterning. Often boundaries
between the different parts of the brain.
> The best‐studied example of this is the isthmic organizer, a group of cells formed close to
the future midbrain–hindbrain boundary. This expresses FGF8 and Wnt1, which diffuse locally
to activate a number of genes. It is required to specify the tectum anteriorly and the
cerebellum posteriorly. Building Brains. Price, Jarman, Mason & Kind, (2017). 2nd edition.
John Wiley & Son Ltd
> The ZLI patterns the diencephalon locally by producing Sonic hedgehog (SHH). Activates the
transcription factor genes Dlx2 on the anterior side and Gbx2 on the posterior side. This
differential response to SHH leads to the formation of the prethalamus and thalamus,
respectively. The basis of this difference depends on the pre‐existing expression of the gene
Irx3 posterior to the ZLI. Building Brains. Price, Jarman, Mason & Kind, (2017). 2nd edition.
John Wiley & Son Ltd
1.2 Brain size control
> Cerebral cortex confers humans with unique cognitive capabilities. Required for all higher
cognitive functions, malformations underlie several neurodevelopmental disorders such as
microcephaly/ macrocephaly, autism spectrum disorders and schizophrenia.
> Size and functional complexity is thought to be behind higher cognitive function of humans
compared to other mammalian species.
-Factors affecting brain size:
> Rate of apoptosis/ programmed cell death
• During development nervous system produces excess of neurons, neurons must make
proper contact with their target cells and if they fail, they are eliminated.
