DEVELOPMENTAL NEUROBIOLOGY
1. Generation of Neurones (then specification of neural cell identity –
neural/glial - and formation of the neural tube and crest)
2. Migration of Neurones
3. Neuronal Growth (projection/ outgrowth of axons towards targets)
4. Axonal Guidance (formation of synapses with targets – neurones,
muscles or gland cells)
(Synaptic connection refinement – elimination of axon branches
and death of excess neurones)
1. THE BIRTH OF NEURONES!
Steps to establishing a neurone in a functioning nervous system:
Neurones develop from other cells in the developing embryo. After the
birth of a neurone, there is…
o Cellular Determination.
o Proliferation
o Cell Migration
o Axonal Project
o Establishment of Connection to target
o Pruning Unnecessary Connections
o Death of Excess Neurones
Brief review of
Development:
The fertilised zygote
divides by mitosis
(cleavage) to create a
blastula, which then
undergoes gastrulation
(complex movement of
cells) to form a 3-
layered gastrula with an
ectoderm (outer layer,
mesoderm (middle
layer) and endoderm
(inner layer). The
ectoderm and
mesoderm and their interactions are required for the formation of the
nervous system.
Determination:
, o Once these cell layers have formed, neuronal cells (will become
neurones or glial cells of the nervous system) are determined.
o Cells of the Ectoderm are “determined” to become neurones by
neural induction. The induction signals largely come from the
mesoderm. Ectodermal cells are subject to inhibitory pathways
which prevent them from becoming neurones – this process is
switched off by molecules released by mesodermal cells, so that
these cells can become neural.
o Once the determination occurs they will either differentiate to
become neurones or remain as a precursor cells. In the adult there
are very few neuronal precursor cells remaining (some in the
olfactory bulb)
o Migration of neuronal precursor cells occur before differentiation to
a neurone is complete.
Organogenesis:
o The different germ cell layers become
rudimentary organs through
organogenesis
o Involves folding, splitting and dense
clustering of embryo
o First rudimentary organs are the neural
tube and the neural crest. In
vertebrate embryos, neurulation is one
of the first events in organogenesis.
o Interaction between ectoderm and
mesoderm results in the formation of the neural plate, which
contains cells that will form 2 structures: the neural tube (which will
become the central nervous system) and neural crest (which will
become cells in the peripheral nervous system, e.g. Schwann cells).
o A third component in the developing nervous system which is
present in the mesoderm is the notochord.
XENOPUS LAEVIS:
o The clawed frog
o Frogs eggs used to study development
o Frog embryo is polar - having a ventral and dorsal surface.
o A region of the ectoderm (animal cap) could be transplanted onto a
second embryo and the frog would grow a second nervous system
o A region of the mesoderm termed the Spemann organiser could also
be transplanted and would cause the formation of nervous tissue.
o The Spemann organiser contains cells that release neural inducers.
o Later studies indicate these are protein such as Noggin, Chordin,
Follistatin and Cerebrus. These factors alter how the ectoderm
develops into the nervous system.
, Formation of axes in frog egg:
a) Animal-Vegetal pole:
b) Dorsal-Ventral axis: this defines
where the nervous system will develop
from
c) Anterior-Posterior axis:
cortical rotation separates
mesodermal and ectodermal
molecules and prevents their
interaction. Where these
determinants do interact, this
forms the Niewkoop centre. This is the focal point at which the
nervous system is generated – it induces the formation of the
Spemann organiser, which establishes the A-P axis.
The Niewkoop centre: around the time of fertilisation, there is a
pigmented animal region and an unpigmented vegetal region, and
maternal factors sit at the bottom of the egg in the vegetal region. The
dorsal side of embryo develops on the opposite side of sperm entry.
Sperm entry causes the outer cortical layer to detach and rotate, causing
1. Generation of Neurones (then specification of neural cell identity –
neural/glial - and formation of the neural tube and crest)
2. Migration of Neurones
3. Neuronal Growth (projection/ outgrowth of axons towards targets)
4. Axonal Guidance (formation of synapses with targets – neurones,
muscles or gland cells)
(Synaptic connection refinement – elimination of axon branches
and death of excess neurones)
1. THE BIRTH OF NEURONES!
Steps to establishing a neurone in a functioning nervous system:
Neurones develop from other cells in the developing embryo. After the
birth of a neurone, there is…
o Cellular Determination.
o Proliferation
o Cell Migration
o Axonal Project
o Establishment of Connection to target
o Pruning Unnecessary Connections
o Death of Excess Neurones
Brief review of
Development:
The fertilised zygote
divides by mitosis
(cleavage) to create a
blastula, which then
undergoes gastrulation
(complex movement of
cells) to form a 3-
layered gastrula with an
ectoderm (outer layer,
mesoderm (middle
layer) and endoderm
(inner layer). The
ectoderm and
mesoderm and their interactions are required for the formation of the
nervous system.
Determination:
, o Once these cell layers have formed, neuronal cells (will become
neurones or glial cells of the nervous system) are determined.
o Cells of the Ectoderm are “determined” to become neurones by
neural induction. The induction signals largely come from the
mesoderm. Ectodermal cells are subject to inhibitory pathways
which prevent them from becoming neurones – this process is
switched off by molecules released by mesodermal cells, so that
these cells can become neural.
o Once the determination occurs they will either differentiate to
become neurones or remain as a precursor cells. In the adult there
are very few neuronal precursor cells remaining (some in the
olfactory bulb)
o Migration of neuronal precursor cells occur before differentiation to
a neurone is complete.
Organogenesis:
o The different germ cell layers become
rudimentary organs through
organogenesis
o Involves folding, splitting and dense
clustering of embryo
o First rudimentary organs are the neural
tube and the neural crest. In
vertebrate embryos, neurulation is one
of the first events in organogenesis.
o Interaction between ectoderm and
mesoderm results in the formation of the neural plate, which
contains cells that will form 2 structures: the neural tube (which will
become the central nervous system) and neural crest (which will
become cells in the peripheral nervous system, e.g. Schwann cells).
o A third component in the developing nervous system which is
present in the mesoderm is the notochord.
XENOPUS LAEVIS:
o The clawed frog
o Frogs eggs used to study development
o Frog embryo is polar - having a ventral and dorsal surface.
o A region of the ectoderm (animal cap) could be transplanted onto a
second embryo and the frog would grow a second nervous system
o A region of the mesoderm termed the Spemann organiser could also
be transplanted and would cause the formation of nervous tissue.
o The Spemann organiser contains cells that release neural inducers.
o Later studies indicate these are protein such as Noggin, Chordin,
Follistatin and Cerebrus. These factors alter how the ectoderm
develops into the nervous system.
, Formation of axes in frog egg:
a) Animal-Vegetal pole:
b) Dorsal-Ventral axis: this defines
where the nervous system will develop
from
c) Anterior-Posterior axis:
cortical rotation separates
mesodermal and ectodermal
molecules and prevents their
interaction. Where these
determinants do interact, this
forms the Niewkoop centre. This is the focal point at which the
nervous system is generated – it induces the formation of the
Spemann organiser, which establishes the A-P axis.
The Niewkoop centre: around the time of fertilisation, there is a
pigmented animal region and an unpigmented vegetal region, and
maternal factors sit at the bottom of the egg in the vegetal region. The
dorsal side of embryo develops on the opposite side of sperm entry.
Sperm entry causes the outer cortical layer to detach and rotate, causing
