Download Ectoderm Germ Layer

Ectoderm Germ
Layer
Frog Fate Map
Frog Fate Map
Role of Organizer Chages in Late
Frog Embryos
Organizer forms three distinct
regions
Notochord formation in chick
Beta-catenin localization
How does beta-catenin become localized to
dorsal side?
Beta-catenin evenly distributed before fertilization.
Dsh and GBP translocated to dorsal side by kinesin
•
•
•
Rides on microtubule tracks laid down after
fertilization during cortical rotation
Dorsal surface enriched in Dsh and GBP
Dsh and GBP inhibit GSK3
–
Beta-catenin degrades on ventral side and is
stabilized on dorsal side
Beta-catenin activates other genes
Turns on goosecoid gene in organizer
Goosecoid mRNA can induce new axis

Activates involution

Determines dorsal mesoderm

Represses Wnt8

Important in brain formation
BMP Gradient Controls
Dorsal/Ventral Axis
VegT and Veg1
Present in vegetal cortical region
Genes required for endoderm and mesoderm
formation
VegT antisence RNA causes epidermis only
Xnr Gradient
High Xnr – Organizer, goosecoid
Med Xnr – Lateral mesoderm
Low Xnr > high BMP4 + Xwnt8 – Ventral mesoderm
Neural ectoderm induced by soluble factor?
Controlled by goosecoid and beta-catenin?
Neural structures default –
epidermis induced by BMP's
BMP – bone morphogenic protein
Induce ectoderm to become epidermis
Organizer secretes factors that block BMP from acting
BMP inhibitors
Noggin, Chordin and Follistatin
Diffusable proteins
Induced dorsal ectoderm to become neural
Dorsalizes mesoderm cells
Inhibits BMP's
Found in dorsal lip then in the notochord
Noggin mRNA rescues
Dorsal Structures
Localization of Noggin
Localization of Chordin mRNA
Expression of paraxial protocadherin
Paraxial protocadherin expression
Blue=paraxial protocadherin
Red=chordin
How is the ant/pos axis determined?
During neurulation beta-catenin forms a gradient
Greatest concentration at organizer
•
Becomes posterior end
BMP Gradient Controls
Dorsal/Ventral Axis
Wnt Gradient Controls
Anterior/Posterior Axis
Gastrulation Induces Nervous
System
Chick Hensen's Node Can Induce
Gene Expression in Frog
Development of Neural Crest
Establishing Neural Cells
•
Competence
•
•
Specification
•
•
Cell have been induced to be neuroblasts, but can
develop into other cells if signals change
Commitment (determination)
•
•
Cell has the capacity to be induced to become
neuroblasts
Neuroblast has entered the neural differentiation
pathway. Cannot be influenced by inhibitory
signals.
Differentiation
•
Neuroblast stop mitosis and express neuron
specific genes.
Wnt/b-catenin
Stem cells from posterior neural
plate form spinal chord
Chick Neural
Tube Closure
Primary neurulation
Directed by cells
adjacent to neural
plate
Anterior
Secondary
neurulation
Split in medullary
chord
Posterior
Chick Neural
Tube Closure
Starts near anterior end
Open at both ends until
fully closed
Anterior and posterior
neuropore
Primary Neurulation
Divides ectoderm into three types of cells
• Neural tube - brain and spinal chord
• Epidermis – skin
• Neural crest cells – peripheral nerves, pigment
cells, glia etc...
Primary
Neurulation
MHP
Medial neural
hinge point
DLHP
Dorsolateral
hinge point
Neural Tube Defects
Spina bifida – failure to close posterior neuropore
Anencephaly – failure to close anterior neuropore
Folate Requirements During
Pregnancy
Folate-binding protein expressed on neural folds
of mouse embryos.
Causes of Folate Related Problems.
Folate deficiency increases chance of neural tube
closure defects in humans.
Most women bearing children with neural tube defects
have antibodies against folate-binding protein.
Fungal contamination of corn produces fumonisin –
alters function of folate-binding protein.
•
Teratogen – substance that alters development.
Role of Cadherins in Neurulation
Neural plate cells switch to N-cadherin expression
just before neurulation.
Injection of E-cadherin mRNA into neural plate
cells or injection of N-cadherin to adjacent cells
alters development
Secondary Neurulation
Medullary cord – condensed mesenchyme cells
Splits to form neural tube
Brain Development
Nervous System
•
•
Central Nervous System (CNS)
•
Brain and spinal cord.
•
Both contain fluid-filled spaces which contain cerebrospinal fluid
(CSF).
•
The central canal of the spinal cord is continuous with the ventricles
of the brain.
•
White matter is composed of bundles of myelinated axons
•
Gray matter consists of unmyelinated axons, nuclei, and dendrites.
Peripheral nervous system.
•
Everything outside the CNS.
•
Spinal and cranial nerves
Somite formation
Derived from the paraxial
mesoderm
Laid down during Hensen's
node regression
Order of somite formation is
predetermined
FGF and Retinoic Acid Gradients
Retinoic Acid Gradient
• Posterior high => Anterior low
• Retinoic acid production at posterior end
–
Retinoic acid degraded at anterior end
Pre-somatic mesoderm has
positional identity
Cdx genes
• Posterior end
– Activated by retinoic acid
• Drosophila caudal gene homologue
• Cdx in conjunctions with other morphogenic
factors activate Hox genes
Hox Genes
• Homeotic gene paralogues
–
Have same basic functions of Drosophila
homeotic genes
• Gene duplication caused multiple copies to
form
• Expressed along dorsal axis
–
–
Neural tube, neural crest, paraxial
mesoderm, surface ectoderm
Anterior boundary of hindbrain to end of tail
Control of Hox Genes Expression
• Partially controlled by retinoic acid and Cdx
genes
– Transcriptional control
Hom and Hox Gene Paralogues
Segment Identity
Which Hox gene are expresses in a particular
segment determines segment identity.
How was this determined?
• Three types of experiments on Hox gene
expression
– Gene “knockout” (deletion)
– Retinoic acid teratogenesis
– Comparative anatomy
Chick and Mouse Vertebral
Pattern
Cervical Thoracic Lumbar Sacral
Mouse
4
13
6
4
Chick
14
7
12/13 5
Comparative Anatomy of Bird
and Mouse Vertebrae
Mice exposed to retinoic acid
•
•
•
•
A,C Normal; B, D Retinoic acid
Defects in facial and cranial skeleton
Missing vertebrae
Deformed pharyngeal arches
Hox C-8 Deletion in Mouse
• First lumbar vertebra
transformed into
thoracic