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74 Cards in this Set
- Front
- Back
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Period of greatest sensitivity to teratogens
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3-8 weeks old embryo
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Ectoderm is one of the 3 primary germinal cell layers in the 2 week old embryo; Induction, Proliferation and Differentiation of Ectoderm into:
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Cutaneous Ectoderm, Neuroectoderm
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Neural tube and cerebral vesicles correspond to
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Central Nervous System (CNS)
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Neural crest and cellular derivatives corresponds to
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Peripheral Nervous System (PNS)
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events in Development of the neural plate
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Primitive (Hensen’s) node
Primitive streak Notochord Three Primary germ layers Ectoderm Mesoderm Endoderm Three Brain regions Forebrain Midbrain Hindbrain |
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During days 15-21 the ectoderm grows and gives rise to what structures
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-Prochordal plates
-Cloacal membrane -Primitve Streak |
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After prochordal plates, cloacal membrane and primitive streak forms, ectoderm growth continues and then it forms
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Neural plate
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After the neural plate is formed, more ectoderm growth occurs and gives rise to
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developing brain
neural groove |
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Growth of mesoderm leads to
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primitive streak epiblast, and hypoblast. Endoderm migrates and stays on top of hypoblast
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After primitive streak and endoderm have been established, mesoderm continues to grow and
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mesoderm grows in between ectoderm and endoderm.
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Notochord development
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it arises from the primitive node on the epiblast and induces the formation of the neural plate and it extends throughout the entire length of the future vertebral column
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Developing brain divides into three parts
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forebrain, midbrain and hindbrain
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As primitive streak grows
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mesoderm and epiblast formed
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notochordal process arises from
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primitive node
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Molecules Important in anterior neurulation are
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Sonic hedgehog (Shh) genes
Bone morphogenetic proteins |
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Sonic hedgehog (Shh) proteins are released by
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notochord ventrally and is responsible for normal dorsal ventral orientation.
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Sonic hedgehog (Shh) proteins are responsible for specific cell types such as
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floor plate cells, ventral motor neurons and interneurons which form due to diffusion and concentration gradients of Shh
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Bone morphogenetic proteins
are released by |
epidernal ectoderm dorsally
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Bone morphogenetic proteins determine
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dorsal structures and cells such as roof plates, neural crest cells and dorsal interneurons
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Bone morphogenetic proteins are a subclass of
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TGFB
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Induction gives rise to
Neurulation gives rise to |
neural plate
neural tube |
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Segmentation defined by
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homeobox Hox genes
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Differentiation (e.g into specific cerebellar or inner ear cells involves
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proneural genes like Atonal (Atoh)
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In which case do bone morphonegenic protens produce anterior neural plate as opposed to the normal cutaneous ectoderm?
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when they are blocked by 3 other genes follistatin, chordin and noggin
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Neurotrophins (Growth factor family) also important for development are mostly found in
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PNS
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Nerve growth factor (NGF) - 1st growth factor discovered
Subsequently found to be specific for only certain classes of neurons (e.g. sympathetic ganglion cells and cholinergic CNS neurons) - receptor is |
TrkA
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Neurotrophins Specific for sensory ganglion neurons
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Brain-derived neurotrophic factor (BDNF) and NT4/5. Receptor is TrkB
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Neurotrophins Specific for all ganglion cells
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Neurotrophin 3 (NT-3). Receptor is TrkC
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Vitamins (Retinoic acid (RA - high concentration in
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Hensen’s node
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Follic Acid (Vit B) important to
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prevent neural tube defects
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Retinoic Acid (Vt A) is important for
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Neural patterning (Differentiation) ~ different parts of nervous system
Gradients of RA important in expression of developmental genes (Hox genes) and in producing posterior neural plate tissue at the expense of anterior NPT. |
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N-CAMs and cadherins important in
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cell migration and axonal outgrowth
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Ephrins
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cell surface signaling molecules important in both axon guidance and in setting up topographic organization.
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Neural tube closure
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Anterior and posterior neuropores are derived from neural fold and primitve streak respectively.
Somites help in segmentation and lead to formation of spinal cord |
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Primary ventricles
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Lateral ventricles
Third ventricles Fourth ventricle |
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Cranial and caudal neuropores
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Amniotic cavity
Neural canal |
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Derivatives of cephalad neural plate
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The cerebral vesicles of the CNS:
Prosencephalon Telencephalon (lateral ventricles) Diencephalon (third ventricle) Mesencephalon (cerebral aqueduct of Sylvius; iter) Rhombencephalon (fourth ventricle) Metencephalon Myelencephalon |
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The prosencephalon has two subdivisions
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-the telencephalon:that will form the cerebral hemispheres
-the diencephalon:that will form optic and thalamic tissues and other structures. |
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The mesencephalon is not subdivided, while the rhombencephalon is divided into
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the metencephalon and the myelencephalon
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In the rhombencephalon, subsegments termed rhombomeres are apparent, as is the
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thin layer of cells at the dorsal-most aspect of this brain region
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Flexures and cerebral vesicles E28
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Cervical flexure
Mesencephalic flexure Pontine flexure and vesicles E3 |
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Rhombomeres and Cranial Nerve Placodes
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Rhombomeres 1-8
Branchial arches Cranial nerve roots derived from placodes Homeobox genes Homeotic mutants |
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Cerebral hemisphere development at E50
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Cerebellum derived from rhombic lip
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Match the vesicles with its correspondent ventricular component
Telencephalon Diencephalon Mesencephalon Metecenphalon Myelencephalon |
Lateral ventricles
Third ventricle Cerebral aqueduct of Silvyis or Iter Fourth ventricle Central Canal |
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Required for normal cerebellar development
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Engrailed (En) and Paired (Pax) genes expressed in gradients peaking at isthmus and rhombic lip
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Required for normal midbrain development
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Fgf8 and Wnt expressed in a ring circumscribing the constriction (isthmus) between the midbrain and the hindbrain
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Required for segmentation of hindbrain and cranial nerve motor nuclei
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Hox 1-8 expressed within brachial arches
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Neuromeres and cerebral vesicles E26
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Neural tube swellings called rhombomeres (r1-r8)
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Rhombomeres defined by
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Homeobox (Hox 1-8) genes 4 copies in humans
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Homeotic mutations lead to
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boundary/segmentation errors
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Rhombomeric boundaries (segmentation) to specific areas related to
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Ephrins and Eph receptors
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Cytodifferentiation/Axon migration
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This proccess refers to the progression in which axons find its proper location in sensory systems depending upon a precise topographic organization
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What molecules are important in axon migration?
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cell adhesion molecules and cell surface molecules such as ephrins
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Lack Patterning genes on the prosencephalon especifically Shh genes lead to
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holoprosencephaly and cyclopia due to failure of the separation of the lobes of the forebrain
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Shh expressed in diencephalon is responsible for
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normal dorsoventral patterning of eyes and cranial neural crest derivatives.
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Why does overexpression of Shh cause defects?
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because normal expression of forebrain genes (Wnt3a, Wnt4, Pax6) is down regulated, while ventral forebrain genes are upregulated
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Cortical areas are also made by differential expression of certain genes which may cause certain people to develop more certain areas of their brain which may explain why some people are
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more visual or more atheltic than others
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During neurogenesis the neuroepithelial cells (multipontential precursors) are found in
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marginal layer
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During neurogenesis Neuroblast and Glioblast are found in
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mantle layer
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During neurogenesis Mitotic cells and ependymal cells (stem cells) are found in
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ventricular layer
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Cytogenesis in Neural Epithelium has two limiting membranes
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External and internal limiting membranes
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Spinal cord neurogenesis leads to
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Neurons derived from neuroblasts
Glia derived from glioblasts Microglia derived from mesenchymal cells Ependymal cells - some remain pluripotential throughout life |
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Glial cells are
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astrocytes (protoplasmic, fibrous)
oligodendroglia microglia |
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Functional morphology and organization of spinal cord neurons
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A cut through the myelencephalon illustrates the thin roof plate as well as the alar and basal plate regions, all of which surround the lumen, which at this level forms the fourth ventricle of the brain
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Ventricular floor arises from
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the spreading of the neural tube walls by the pontine flexures so that they and the sulcus limitants make the ventricular floor
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The tissue of the metencephalon will form the
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cerebellum and the pons
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Derivatives of the neural crest
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Dorsal root ganglion
Pseudounipolar ganglion cells Satellite cells Schwann cells (for peripheral myelin) Postganglionic sympathetic visceral efferents Adrenal medulla (chromafin cells) Postganglionic parasympathetic visceral efferents |
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Hirschsprung's disease (congenital megacolon)
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No parasympathetic ganglia due to failure of neural crest cell migration
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Spina Bifida Oculta
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In occulta, the outer part of some of the vertebrae are not completely closed.[2] The split in the vertebrae is so small that the spinal cord does not protrude. The skin at the site of the lesion may be normal, or it may have some hair growing from it (tuft of hair) ; there may be a dimple in the skin, or a birthmark.
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Meningocoele
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The least common form of spina bifida is a posterior meningocele (or meningeal cyst).
In a posterior meningocele, the vertebrae develop normally, however the meninges are forced into the gaps between the vertebrae. As the nervous system remains undamaged, individuals with meningocele are unlikely to suffer long-term health problems, although there are reports of tethered cord |
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Meningomyelocoele
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This type of spina bifida is the most common and often results in the most severe complications.[11] In individuals with myelomeningocele, the unfused portion of the spinal column allows the spinal cord to protrude through an opening. The meningeal membranes that cover the spinal cord form a sac enclosing the spinal elements.
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Spina bifida with myeloschisis
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Spina bifida with myeloschisis is the most severe form of myelomeningocele. In this type, the involved area is represented by a flattened, plate-like mass of nervous tissue with no overlying membrane. The exposure of these nerves and tissues make the baby more prone to life-threatening infections
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Pax-3 null mutants exhibit
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spina bifida, lack of dorsal root ganglia and neural crest derivatives
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questions to keep in mind
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Neural crest arises from what layer of the embryo, and gives rise to what cells in the PNS, in the gut and in the skin?
During development of the CNS we speak of "encephalization", what does this mean? Describe the derivatives of the prosencephalon and rhombencephalon. Failure to close the anterior neuropore would take place at what embryonic age, and result in what clinical syndrome? Why is Vitamin A important for normal development? Describe three gene products important for normal morphogenesis? |
