Neurodevelopment Flashcards
Define Gastrulation
- day 13-19
Process during embryonic development that changes the embryo from a blastula with a single layer of cells to a gastrula containing multiple layers of cells.
During gastrulation, the blastula folds in on itself and cells migrate to form the three layers of cells in which strucutre?
The gastrula, with a hollow space that will become the digestive tract
Three Germ Layers
1) Ectoderm (outer layer)
2) Mesoderm (middle layer)
3) Endoderm (internal layer)
How is the blastula formed?
Single cell zygote which undergoes rapid cell division, called cleavage to form a hollow ball of cells called a blastula
In mammals, what does the blastula forms in the next stage of development?
blastocyst
How are the cells in the blastula arranged in the blastocyst?
Arrange themselves in two layers: the inner cell mass, and an outer layer called the trophoblast.
What does the inner cell mass do?
Forms the embryo
What does the ectoderm give rise to?
Nervous system and the epidermis, among other tissues, neural crest
Mesoderm
Gives rise to the muscle cells and connective tissue in the body, digestive tract, red blood cells, and the tubules of the kidneys,
Endoderm - gives rise to tissues that form internal structures and organs.
the colon, the stomach, the intestines, the lungs, the liver, and the pancreas.
Difference between the development of a fish and mice?
Fish develop outside of the body, mice develop inside the belly
Organogenesis
Three germ layers of the embryo differentiate and further specialize to form the various organs of the body
Primitive Streak
Temporary structure whose formation, on day 15 of human development, marks the start of gastrulation,
What does the primitive streak give rise to?
The notochord and to the third basic layer, the mesoderm.
Notochord
flexible rodlike structure of mesodermal cells that is a defining strucutre in chordates and has an essential role in vertebrate development
What does the notochord define?
The embryonic midline, and thus the axis of symmetry for the entire body.
Neuroectoderm
Consists of cells derived from the ectoderm, formation of neuroectoderm is the first step in the development of the nervous system
Neural Plate
Thickened portion of ectoderm along the midline of the embryo
Neurlation
Formation of the neural tube from the ectoderm of the embryo.
Structures Present on Day 18 (5)
- Three Germ Layers
- Primitive Streak
-Neuroectoderm - Notochord
- Neural Plate
Day 20 Structures (6)
- Neural Plate/tube
- Neural Crest
- Neural Groove
- Pre-somatic mesoderm
- Floorplate
- Notochord
Neural Crest
Group of embryonic cells that are pinched off during the formation of the neural tube
Floorplate
critical signaling center during neural development located along the ventral midline of the embry
Day 22 Structures
Notochord
Neutral Tube
Neural Crest
Anterior Neural Fold
Somite
Floor Plate
Roofplate
What structure is required to form the peripheral nervous system?
Neutral Crest
Rhombencephalon (brain stem/cerebellum)
- region of the developing vertebrate brain that is composed of the medulla oblongata, the pons, (brain stem) and the cerebellum.
Spina Bifida
Birth defect in which an area of the spinal column doesn’t form properly, leaving a section of the spinal cord and spinal nerves exposed.
Two types of Spina Bifida
1) Spina Bifida Occulta (Hidden)
2) Spina Bifida Aperta (Visibly present)
Complication of Spina Bifida (4)
Neurological complications
Executive function
Academic skills
Social complications
Anterior Part of Neural Tube (3)
1) Forebrain
2) Midbrain
3) Hindbrain
Interior of Neural Tube
Fluid filled central cavities
Central Canal of the spine
Prosencephalon
- become the cerebrum, thalamus, hypothalamus, pituitary gland, limbic system, and the olfactory bulb
What vesicles further divide to form secondary vesicles?
Prosencephalon and Rhombencephalon
Derived Brain Structures of Telencephalon
Cerebral hemispheres
telencaphlon cavity
Lateral ventricles
Derived Structures of the Diencephalon
Thalamus, hypothalamus, eye, cerebral peduncles, quadrigeminal plate)
Diencaphlon cavity
Third ventricle
Derived Brain Structures Metencephalon
Pons, cerebellum
Metencaphlon, Myelencephalon cavity
Fourth ventricle
Derived Brain Structure and Cavities Myelencephalon
Medulla oblongata + Fourth ventricle
Cervical Flexure
The junction between the hindbrain and the spinal cord
Cephalic Flexure
Flexure is in the midbrain.
Pontine Flexure
Forms the boundary between the metencephalon and the myelencephalon.
What do you need to execute gene function?
Transcription factors
Transcription factors
Proteins involved in the process of converting, or transcribing, DNA into RNA.
What does a way a gene is read and at what time depend on?
What type of transcription factors are available at a particular time and has access to a particular gene
Enhancers
Activate transcription factors
Promotor
Region of DNA where transcription of a gene is initiated
Hox Genes
Group of relate genes that specify regions of the body plan of an embryo along the head-tail axis of animals
Where are hox genes located in most animals, including humans?
Follows the 3′-to-5′ orientation of these
genes on their respective chromosomes
How are hox genes positioned?
Anterior-to-posterior
Protein phosphorylation
Important cellular regulatory mechanism as many enzymes and receptors are activated/deactivated by phosphorylation
Cell impermeant Molecules
Molecules that are unable to cross the lipid bilayer plasma membrane and must therefore bind to extracellular receptors (interact with transmembrane receptors)
How are hox genes turned on?
By a cascade of regulatory genes; the proteins encoded by early genes regulate the expression of later genes.
Three Steps of Primary Neuralation
1) Formation/shaping of the neural plate;
2) Bending of neural plate to form the neural groove;
3) Closure of the neural tube
What structures do primary and secondary neurulation form?
Primary- cranial structures
Secondary= caudal structures
How does primary vs secondary neuralation occur
primary= anterior to posterior (rostral- caudal)
secondary = posterior
What is primary neuralation
Process by which the neural tube, the precursor of the brain and spinal cord, is shaped from the neural plate
What is secondary neurulation
The neural ectoderm cells hollow out to form the neural tube.
Steps of Secondary Neurulation
1) Neural ectoderm and some cells from the ectoderm form the medullary cord
2) The medullary cord condenses, separates and then forms cavities
3) These cavities then merge to form a single tube
4) Tubes from both primary and secondary neurulation eventually connect at around the sixth week of development
What does primary neurulation occur in response to?
Soluble growth factors secreted by the notochord
How do the shape of cells changes during primary neurulation?
The cells of the neural plate are signaled to become high-columnar, move laterally and away from the central axis
How does the notochord play an important role during development?
Serves as a midline tissue that provides directional signals to surrounding tissue during development,
What will non-ectoderm tissue form into?
Mesoderm surrounding the notochord at the sides will develop into somite (future muscles, bones, and contributes to the formation of limbs of the vertebrate)
Reelin
Gene that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions.
Gila Endfoot
- Releases soluble factor reelin which creates a gradient and the neurons have several receptors to read info about how much reelin is aviable and will go for max contact with reelin
- They will climb for as a long as they can find rln
How is Reelin Mutation Caused?
The signaling pathway that triggers neuronal migration is not activated
What happens without reelin?
Neurons are disorganized, the normal folds and grooves of the brain do not form, and brain structures do not develop properly.
Lissencephaly
Smooth brain that has an absence of folds, caused neuron migration being disturbed
Dysfunction of sonic hedhog
no separation of hemispheres, affects internal formation and how skull is formed and eye
- look like cyclops
Neurogenesis
Undifferentiated cells (neural stem and progenitor ) undergo mitotic division to produce either new stem cells or neuroblasts that will eventually differentiate into neurons
What signals do the roof and floorplate send out?
- signals to instruct the neurons along the newly forming neural tube and spinal cord
How does cell migration play a role in the developing cortex?
Cell migration has an essential role in the developing cerebral cortex because all neurons that eventually populate the six-layered cerebral cortex and other brain regions undergo mitosis in distant areas and then migrate great distances to achieve final positioning.
Cell Impermanent Molecules
Molecules that are unable to cross the lipid bilayer plasma membrane and must therefore bind to extracellular receptors (interact with transmembrane receptors)
Cell Permeant Molecules:
Molecules that are relatively insoluble and are able to cross the lipid bilayer plasma membrane to bind to intercellular receptors
- These intercellular receptors will cross into the nucleus through one of the nuclear pores
What happens once the intercellular receptors cross into the nucleus?
-Activate transcription programs and bind to promotor activating genes
Cell Associated Molecules
Exposed at the cell surface and they can bind to another protein which is coming from the other side and by doing so they can activate receptors on the other side and initiating signaling pathways
Difference between an indirect vs direct soluble factor
Indirect soluble factor requires a receptor in between
Major Inductive Signaling Pathway: Retinoic Acid
Soluble Factor & Direct
- RA cross the membrane and active R.A binding proteins directly which can activate transcription
Major Inductive Signaling Pathway: Fibroblast Growth Factor (FGF)
Soluble factor and receptor kinase
- soluble factor finds a specific partner (receptor) and initiates a specific pathway
Major Inductive Signaling Pathway: Bone Morphogenetic Protein (BMP)
Soluble factor and receptor kinase (indirect)
- BMP is released into extracellular space by exocytosis, it has to bind to the serine kinase and activate a signalling pathway
Major Inductive Signaling Pathway: Non- Canonical Wnt
Soluble factor and receptor signaling pathway
- Here Wnt ligands activate receptor proteins (Frizzled), or binds to orphan receptor tyrosine kinase, leading to the activation of a signaling pathway
Major Inductive Signaling Pathway: Canonical Wnt
Soluble factor and receptor signaling pathway
Major Inductive Signaling Pathway: Sonic Hedge
Soluble factor & receptor with adaptor protein
- Sonic hedhog doesn’t interact with the receptor but it has a protein complex that interacts with the patch protein
- The patched protein itself cannot trigger a signal, it requires another protein which is recruited upon activation
- Then you get activation of a signalling protein
Steps of Neurogenesis (2)
1) The cells undergo a type of pattern as they progress through the mitotic cycle, eventually the dividing precursor cells from a closely packed layer of cells called the ventricular zone
2) Some cells leave the ventricular zone and form the marginal zone, later an intermediate zone develops
What type of cells are formed in the intermediate zone?
Neurons and radial gila
Cell migration
The movement of cells (which are being formed during the ongoing process of neurogenesis) along the radial glia toward the marginal zone from the ventricular zone
Radial gila
Allow cells which are formed in the ventricular zone to climb upwards towards the cortical plate
Cell Differentiation
Neurons differentiate into specific neurons and glial cells
