Chapter 10 - Emergence of the ectoderm Flashcards
The vertebrate ectoderm (outer germ layer covering the late-stage gastrula) has three major responsibilities:
- One part will become neural tissue and the central nervous system.
- Another part will become the epidermis.
- Between these two lies the neural crest.
Epidermis
the largest organ of the vertebrate body. The epidermis forms an elastic, waterproof, and constantly regenerating barrier between the organism and the outside world.
Neural crest
lies between the compartments forming the epidermis and CNS. These cells migrate away from the dorsal centre of the embryo to generate, among other things, the PNS and melanocytes.
Neurulation
the process by which the three ectodermal regions are made physically and functionally distinct from one another. Follows directly after gastrulation.
Neurula
an embryo undergoing neurulation.
The specification of the ectoderm is accomplished primarily by regulating the levels of BMP experienced by the ectodermal cells.
High BMP => epidermis
Very low => neural plate
Intermediate => neural crest
The cells of the neural plate are characterized by expressing the Sox family of TFs (Sox1, 2, and 3), they:
- Activate the genes that specify cells to be neural plate
- Inhibit the formation of epidermis and neural crest by blocking the transcription and signalling of BMPs.
This expression establishes the neural plate cells as neural precursors that can form all the cell types of the CNS.
Formation of the neural tube, accomplished in two major steps:
- Primary neurulation:
- Secondary neurulation:
- The complete neural tube forms by joining these two together. Varies with species where line between the two is.
Primary neurulation:
the cells surrounding the neural plate direct the neural plate cells to proliferate, invaginate into the body, and separate from the surface to form a hollow tube. Generally anterior method.
Secondary neurulation:
the neural tube arises from the coalescence of mesenchyme cells into a solid cord that subsequently forms cavities that coalesce to create a hollow tube. Generally posterior method.
Primary neurulation can be divided into four distinct but spatially and temporally overlapping stages:
- Extension and folding of the neural plate – divisions of the neural plate cells are preferentially in the AP direction. They occur even if the neural tissue is isolated from rest of the embryo. However, in order to roll into a neural tube, the presumptive epidermis is needed.
- Bending of the neural plate – Involves the formation of hinge regions where the neural plate contacts surrounding tissues. In birds + mammals, the cells at the midline of the neural plate form the medial hinge point (MHP), which becomes anchored to the notochord beneath and form a hinge, which forms a furrow at the dorsal midline. Notochord induces MHP cells to decrease in height and become wedge-shaped (pulling the midline down in a ”V” shape).
- Convergence of the neural folds – two dorsolateral hinge points (DLHPs) are induced by the non-neural ectoderm and anchored to the surface (epidermal) ectoderm. The cells elongate and become wedge-shaped. After the initial furrowing (2.) the plate bends around the hinge regions. The surface ectoderm also pushes toward the midline, providing additional motive force for bending the neural plate, causing the neural folds to converge toward each other. This movement and the anchoring may also be important in ensuring the neural tube invaginates inward instead of folding out.
- Closure of the neural tube – The neural tube closes as the folds are brought together at the dorsal midline. The folds adhere to each other, and the cells from the two sides merge.
Events of neural tube closure
Closure of the neural tube does not occur simultaneously throughout the ectoderm., fx occurs A->P (amniote vertebrates), starts in middle and ”zips up” in both directions (chicks), or closure is initiated at several places (humans).
The two open ends of the neural tube are called the anterior neuropore and the posterior neuropore.
Amniote vertebrates
reptiles, birds, and mammals
Neural tube closure defects - Spina bifida
failure to close the posterior neuropore around day 27 of development, severity depends on how much of the spinal cord remains exposed.
Neural tube closure defects - Anencephaly
lethal failure to close site 2 / 3, keeps the anterior neuropore open, resulting in the forebrain remaining in contact with the amniotic fluid which subsequently degenerates. The fetal forebrain ceases development, and the vault of the skull fails to form.
Neural tube closure defects - Craniorachischisis
the failure of the entire neural tube to close over the body axis.
Failure to close the neural tube can result from both genetic and environmental causes.
It has been estimated that more than half of all human neural tube birth defects can be prevented by pregnant women taking supplemental folate.
Secondary neurulation
Secondary neurulation involves the production of mesenchyme cells from the prospective endoderm and ectoderm.
Followed by the condensation of these cells into a medullary cord beneath the surface ectoderm.
After this mesenchymal-epithelial transition, the central portion of this cord undergoes caviation to form several hollow spaces or lumens; the lumens then coalesce into a single central cavity.
Differentiation of the neural tube into the various regions of the brain and spinal cord occurs simultaneously in three different ways.
- On the gross anatomical level, the neural tube and its lumen bulge and constrict to form the chambers of the brain and spinal cord.
- At the tissue level, the cell populations in the wall of the neural tube arrange themselves into the different functional regions of the CNS.
- On the cellular level, the neuroepithelial cells themselves differentiate into the numerous types of nerve cells (neurons) and associative cells (glia) present in the body.
The DV axis
The neural tube is polarized along its DV axis. In the spinal cord, fx, the dorsal region is the place where the spinal neurons receive input from sensory neurons, whereas the ventral region is where the motor neurons reside. In the middle are numerous interneurons that relay information between the two.
The DV polarity of the neural tube is induced by signals coming from its immediate environment. Ventral imposed by (Sonic hedgehog protein) notochord, dorsal induced by (TGF-beta) overlying epidermis.
Neurons
conduct electric potentials and coordinate our bodily functions, our thoughts, and our sensations of the world.
Glial cells
aid in constructing the nervous system, provide insulation around the neurons, and may be important in memory storage.
Dendrites
the fine branching extensions of the neuron that are used to pick up electric impulses from other cells. Some neurons develop only a few, whereas others develop extensive, branching dendritic arbors.
Synapses
connections with other neurons
Axon
a continuous extension of the nerve cell body, may extend 2-3 feet
Soma
neuronal cell body
Glial guidance
mechanism thought to be important for positioning young neurons in the developing mammalian brain. Neurons ride a ”glial monorail” to their respective destinations.
Growth cone
tip of the axon that leads nerve outgrowth by ”feeling” its way along the substrate. Moves by elongation and contraction of pointed filopodia (microspikes). Each microspike samples the microenvironment and sends signals back to the soma
The adult brain is capable of producing new neurons, unlike what was previously thought. Environmental stimulation can increase the number of these new neurons.
Productions of neurons in adults appears to be limited to
- The subventricular zone along the walls of the lateral ventricles
- Certain regions of the hippocampus.
- Type of neuron produced is determined by the paracrine factors (Sonic hedgehog particularly important) that are secreted by other cells in the neighbourhood.
The adult stem cells are not multipotent(?). And proliferate in response to exercise, learning, and stress.
Within the axon itself, structural support is provided by microtubules, and the axon will retract if the neuron is places in a solution of colchicine (inhibitor of microtubule polymerization).
Elongation by microtubules and apical shape changes by microfilaments.
The exploratory microspikes of the growth cone attach to the substrate and exert a force that pulls the rest of the cell forward. Axons will not grow if the growth cone fails to advance.
To prevent dispersal of the electric signal and to facilitate conduction to its target cell , the axon is insulated at intervals by glial cells.
In CNS – oligodendrocytes wrap themselves around the developing axon, then produce a specialized cell membrane called a myelin sheath.
In PNS – myelination is accomplished by Schwann cells (a glial cell type)
Sheath diameter is regulated by the amount of neuregulin-1 secreted by the axon
Myelin sheath is essential for nerve function and keeps the axons alive for decades
Lens placode
eye develops from here. Does not form neurons, but rather the transparent lens that allows light to impinge on the retina.
Neurotransmitters
small signalling molecules used to affect target cell
Eye development:
- The optic vesicle evaginates from the brain and contacts the overlying ectoderm, inducing a lens placode.
- The overlying ectoderm differentiates into lens cells as the optic vesicle folds in on itself (forming the two-layered optic cup, drawing the developing eye into the embryo), and the lens placode becomes the lens vesicle.
- The optic vesicle becomes the neural (inner layer) and pigmented retina (outer layer) as the lens is internalized.
- The lens vesicle induces the overlying ectoderm to become the cornea.
Synaptic cleft
small gap that separates the axon of a signalling neuron from the axon/surface of its target cell.
Axons are specialized for secreting specific neurotransmitters across the synaptic cleft.
Tissue architecture of the CNS
The neurons of the brain are organized into layers (laminae) and clusters (nuclei), each having different functions and connections.
Too much Sonic hedgehog
=> no eyes
Lens and cornea differentiation
The differentiation of lens tissue into a transparent membrane capable of directing light onto the retina involves changes in cell structure and shape as well as the synthesis of transparent, lens-specific proteins (crystallins).
As the lens cells continue to grow, they synthesize crystallins, which eventually fill up the cell and cause the extrusion of the nucleus.
The lens contains 3 regions:
- An anterior zone of dividing epithelial cells
- An equitorial zone of cellular elongation
- A posterior + central zone of crystallin-containing fibre cells.
Intraocular fluid pressure
(From the aqueous humor) is necessary for the correct curvature of the cornea, allowing light to be focused on the retina.
Neural retina differentiation
Layers of different neuronal types includes the light- and colour-sensitive photoreceptor cells (rods and cones); the cell bodies of the ganglion cells; and bipolar interneurons that transmit electric stimuli from the rods and cones to the ganglion cells.
In addition, the retina contains numerous Müller glial cells that maintain its integrity, amacrine neurons (which lack large axons), and horizontal neurons that transmit electric impulses in the plane of the retina.
Signal pathway
Rods and cones => bipolar nerve => ganglion cells => optic nerve fibres (ganglion axons)
But light passes through the layers from optic nerve end to rods and cones at the bottom.
Not all the cells of the optic cup become neural tissue
The tips of the optic cup on either side of the lens develop into a pigmented ring of muscular tissue (iris).
Iris muscles control the size of the pupil.
Subventricular zone
immediately adjacent to ventricular zone, each progenitor cell (transit amplifying cells!) divide symmetrically here
Mammalian skin has 3 major components:
- A stratified epidermis
- An underlying dermis composed of loosely packed fibroblasts
- Neural crest-derived melanocytes that reside in the basal epidermis and hair follicles
- (In addition a subcutaneous fat layer present beneath the dermis)
White matter
marginal zone, white pga myelin sheath on axons
Periderm
a temporary covering that is shed once the inner layer differentiates to form a true epidermis
Basal layer / stratum germinativum
contains epidermal stem cells attached to a basal lamina that the stem cells themselves help to make
Keratinocytes obtain their pigment through
the transfer of melanosomes from the processes of melanocytes that reside in the basal layer
Cell division from the basal layer produces
younger cells and pushes the older cells to the border of the skin.
Keratinocytes
differentiated epidermal cells that have ceased transcriptional and metabolic activities, bound tightly together, producing a water-impermeable seal of lipid and protein
Cornified layer / stratum corneaum
constituted of dead, flattened sacs of protein cells with their nuclei pushed to one edge
Humans lose 1.5 g of dead keratinocytes from the cornified layer each day
The cutaneous appendages: mammalian hair
The epidermis and dermis interact at specific sites to create the sweat glands and the cutaneous appendages: hair, scales, scutes (fx turtle shells), or feathers.
The formation of these requires a series of reciprocal inductive interactions between the dermal mesenchyme and the ectodermal epithelium, resulting in the formation of epidermal placodes (thickenings) that are the precursors of hair follicles.
Epidermal cells in the region capable of forming placodes secrete Wnt protein, which is critical for initiation of follicle development.
Astrocyte
adult glial cell
The dynamics of optic development: the vertebrate eye
The major sensory organs of the head develop from interactions of the neural tube with a series of epidermal thickening (cranial ectodermal placodes).
Types of hair (human):
- First in embryo prior to birth: lanugo – thin, closely spaced, shed before birth
- Lanugo replaced with vellus hair (at least partially due to new follicles), short and silky. Remains on many parts of the human body usually considered hairless, fx forehead and eyelids
- ”Terminal” hair, replaces vellus hair, longer and thicker.
During a person’s life, some of the same follicles that first produce vellus hair later form terminal hair and still later revert to vellus hair production
There appear to be 3 stem cell populations involved in producing epidermal structures:
- Found in germinal layer, generates the keratinocytes that characterizes the interfollicular epidermis
- Critical for forming the sebaceous gland of each hair shaft
- Critical for regenerating the hair shaft itself
- (Primitive stem cell that can form all the above) Though members of each group can be recruited to any of the others
Hair follicles undergo cycles
of growth (anagen), regression (catagen), rest (telogen), and regrowth.
Hair length is determined by the amount of time the hair follicle spends in the anagen phase, fx scalp hair = years whereas arm hair 6-12 weeks.
Bulge region in hair follicle contains at least two remarkable adult stem cells:
- Hair follicle stem cells (HFSCs), gives rise to the hair shaft and sheath
- Melanocyte stem cells, gives rise to the pigment of the skin and hair
The retina develops from a bulge in the forebrain.
The interactions between the lens placode cells and the presumptive retina structure the eye via a cascade of reciprocal changes that enable the construction of an intricately complex organ.
The activation of the head ectoderm’s latent lens-forming ability and the positioning of the lens in relation to the retina are accomplished by the optic vesicles that extend from the diencephalon of the forebrain.
Formation of the eye field: the beginnings of the retina
Pax6 initiates a cascade of TFs with overlapping functions. These factors mutually activate one another to generate a single large, eye-forming field in the venter of the ventral forebrain.
The main player in separating the single vertebrate eye field into two bilateral fields is Sonic hedgehog. Sonic Hedgehog from the prechordal plate suppresses Pax6 expression in the centre of the neural tube, dividing the field in two.
Cyclopia
a single eye in the centre of the face, usually below the nose, as a result of mutated Sonic hedgehog (gene or protein).
Skin
the largest organ in our bodies, though, elastic, water-impermeable membrane
Regenerative ability is due to population of epidermal stem cells that last the lifetime of our bodies.
Origin of the epidermis
Epidermis originates from the ectodermal cells covering the embryo after neurulation.
Induced to form epidermis rather than neural tissue by the actions of BMPs.
First only one cell layer thick
Soon becomes two-layered
Outer gives rise to periderm
Inner = basal layer / stratum germinativum
Hair follicles and hair generation in mammals
- Aggregation of cells in the basal layer directed by the underlying dermal fibroblast cells is the first step in placode formation, can occur at different times and different places in the embryo
- The basal epidermis cells elongate, divide and sink into the dermis
- The dermal fibroblasts respond by forming a small node (dermal papilla) beneath the hair germ.
- The dermal papilla pushes up on the basal stem cells and stimulates them to divide more rapidly
- The basal cells respond by producing post-mitotic cells that will differentiate into the keratinized hair shaft
Hair formation:
- Once placodes are established, signals from each induce clumping of underlying dermal fibroblasts, forming a dermal condensate.
- Reciprocal signalling between the condensed dermis and the epithelial placode causes the placode tissue to proliferate and extend downward into the dermis.
- Eventually the epithelium surrounds the dermal condensate, which develops into the hair follicle dermal papilla, an important signalling centre in the mature hair follicle.
- Further proliferation and differentiation of the epithelial cells result in the formation of the inner root sheath and hair shaft of the mature follicle, processes that are likely to require lateral communication between epithelial cells.
- As the hair follicle matures, an epithelial swelling begins to form on the periphery of the hair germ and eventually develops into the sebaceous gland.
Sebaceous glands
produce an oily secretion known as sebum that functions to lubricate the hair follicles and skin, found in periphery of hair follicle, near epidermal surface
Hair cycle:
The HFSCs are activated at the beginning of anagen phase by signals from the nearby dermal papilla of condensed mesenchyme.
These signals direct the epidermal stem cells to migrate out of the bulge.
There, they produce transit amplifying cells that proliferate downward and generate the seven concentric columns of cells that form the outer root sheath from bulge to matrix.
This activation of the dermal papilla appears to be regulated by the microenvironment of the dermis.
As the dermal papilla is moved farther away by the growth of the sheath cells, its signal are not received by the hair germ (in bulge region?), and the hair germ return to quiescence
During the latter part of anagen, prostaglandins prevent the production of transit amplifying cells.
During catagen most of the hair shaft cells undergo apoptosis, however the upper follicular stem cells remain.
The apoptosis causes the outer cells to be in contact with the dermal papilla once again, in readiness for the next cycle of activation.
