Bio 127 Lecture Section 3—Organogenesis Part 1
Ch. 9 Stem Cell Intro
I) Stem Cell Role in the Development of Tissues and Organs
-Gastrulation produces the 3 germ layers
-Interaction of germ layers induces organogenesis
-Stem cell and niche important in organogenesis
A) The Stem Cell Concept
1) Division produces one new stem cell and one daughter; sometimes both stem cells
2) Organs where divisions frequently replenish: gut, epidermis, bone marrow
3) In some cases stem cell only divide due to stress or to repair organ: heart, prostate
B) Terminology
1) Totipotent: zygote and 4-8 blastomeres. Can form trophoblast cells and embryo cells
2) Pluripotent: able to give rise to cells that develop from the 3 germ layers. ESC
3) Commited
(i) Multipotent: Adult stem cells, hematopoietic, mammary, gut
(ii) Unipotent: adult stem cells, spermatogonia, melanocyte
C) Types
1) Embryonic Stem Cells
(i) Derived from inner cell mass
2) Adult Stem Cells
(i) Limited potential, hard to extract and culture
3) Mesenchymal Stem Cells
(i) Surprising degree of differentiation plasticity
(ii) Found in lots of niches in both embryo and adult
(iii)Migrate from niche to provide paracrine stimulus to repair injured tissues
II) Stem Cell Niche
-Microenvironments where cells that stay remain undifferentiated. Those that leave
differentiate
A) Hematopoietic stem cells and the bone marrow niche
1) Hematopoeitic stem cell generates second stem cell capable of becoming a
lymphocyte or myeloid progenitor cell
2) Types of cells in niche secrete factors affecting differentiation
B) The mouse tooth stem cell niche (not in human)
1) positive – negative balance of FGF3 - BMP4 and activin - follistatin
C) Stem cell niche in Drosophila testes
1) Hub cells secrete unpaired protein initiating Jak-Stat leading to stem cell division
2) Cells in contact with hub cells remain stem cells
3) Cadherins hold first centrosome close to hub
D) Niche Breakdown and Aging
1) Too much differentiation deplete capacity for renewal
2) Too much cell division—cancers
Ch9. The Emergence of the Ectoderm
I) Neurulation: Process going from gastrulation to intact nervous system
A) Two Steps
1) Induction of neural cells leading to neural tube
2) Differentiation of neurons
B) Secreted factors from notochord cause neurulation in ectoderm
C) Primary neurulation
1) Events divide ectoderm into 3 sets of cells: neural tube from neural plate, epidermis,
and neural crest
2) Cells surrounding neural plate tells neural plate cells to proliferate, invaginate, and
form hollow tube
(i) Pinching off accomplished by switching of neural plate cells from E-cadherin
adhesion proteins to N-cadherin
(ii) Neural crest cells transition from epithelial to mesenchymal and migrate away
D) Secondary neurulation
1) involves condensation of mesenchyme followed by apoptosis to hollow out tube
E) Primary and secondary neurulation combine to form neural tube
F) Human neural closure: 3points of closure
1) Neural folds adhere and cells merge
2) In amniotes neuralation occurs from anterior to posterior
3) Closure failure leads to spinal bifida (posterior neuropore), anencephaly (anterior
neuropore), and carniorachischisis (whole tube)
4) Folate supplements can reduce neural defect
(i) Folate binding proteins located at points of neural tube closure
II) Differentiation of the Neural Tube
A) Three simultaneous levels of development
1) Gross anatomy: bulges and constrictions form chambers of brain and spinal chord
2) Tissue anatomy: cells in wall rearrange to form different functional regions
3) Cell biology: neuralepithelial cells differentiate into neurons and glia
B) Two simultaneous axis of development
1) Anterior-Posterior
2) Dorsal-Ventral
(i) Polarized. Dorsal region associated with sensory neurons. Ventral region with
motor neurons.
(ii) Controlled by Shh from notochord (ventral) and TGF-B from dorsal ectoderm
C) Early Brain Development
1) Osmotic sodium gradient cause water to fill presumptive ventricles
2) Cavity size of brain to increase due to pressure
3) Occlusion of neural tube facilitates brain expansion
4) Brain size determined by size of cavity, not tissue growth
III)
Differentiation of Neurons in the Brain
A) Neuroepithelium starts as one layer of stem cells
1) give rise to ependymal cells, neurons, and glia
B) Actin microspikes of growth cones senses invironment and migrates cell
C) Myelination
1) In the central nervous system, oligodendrocyte cells wrap around axon
2) In the peripheral nervous system Swhwann cells wrap around the axon
3) Demyelination causes convulsions, paralysis, and multiple sclerosis
IV) Tissue Architecture in th e Central Nervous System
A)
B)
C)
D)
E)
Neurotube starts out 1 layer thick germinal neuroepithelium
Nucleus position depend on cell cycle
Stem cell divisions are horizontal while differentiating cells from vertical divisions
Anterior posterior dorsal ventral affect neural function, transmitter type and connections
Complexity increases anteriorly
V) Development of the human spinal cord
A) Neural tube differentiate into 3 adult layers
1) Ependema (ventricular zone), mantle (intermediate) , and mylin layer (marginal)
VI) Differentiation of Cerebellum
A) Adds 3 additional layers
1) Purkinje layer, inner and outer granular layers
B) Neurons migrate along glia processes
VII) Cerebral cortex is most complex
A) formation of neocortex
1) six layers
2) adult form not completed until mid childhood
3) organized dorsal-ventral and anterior posterior
VIII) Development of Sensory Systems
A) Form from cranial ectodermal placodes
B) Made competent by endo meso signals
C) Lens placode
1) Reciprocal induction between neural tube and ectoderm
(i) Optic vesicle evaginates and contact ectoderm
(ii) Delta and notch binding
D) Lens induction cause cells to elongate and invaginate
1) Moves inward by attaching filopedia to optic vesicle cells
E) Lens signals cause 2 layers of optic cups to form pigment and retina
F) Lens tissue induced to make crystalline
IX) Key Differentiation Events
A)
B)
C)
D)
E)
F)
Occular tissue does not develop without retinal homeobox gene
Neural retina forms 7 major layers of neurons
Iris controls pupil dilation and eye color
Neural crest mesenchyme forms cornea
Shh separates eye field into bilateral fields
Too much Shh and eye field don’t form
X) Epidermis and Its Cutaneous Appendages
A) Layers of the epidermis
1) Same design as neuroepithelium
2) Outer layer composed of dead cells
3) Inner layer divides through life
4) Daughter cells differentiate into keratinocytes
(i) Keratinocytes stop their metabolism and dye to form protective layer
B) Reciprocal induction in development of hair follicles
1) Dermal fibroblast induce placode formation. Placode in turn induce dermal fibroblast
to form dermal papilla fibroblasts
2) Dermal papilla induces stem cell daughters to differentiate
3) Bulge is stem cell niche for basal cells and melanocytes
C) Even hair spacing due to epithelium secretion of wnt10 and dickkopf
1) Wnt causes autocrine formation of placodes
2) Dickkopf is wnt inhibitor
Ch 10 Neural Crest Cells and Axonal Specificity
The Neural Crest
-Neural crest unique to vertebrates
-Specified along anterior-posterior axis into four regions: cranial, cardiac, trunk, vagosacral
-Most cells progenitors or determined
-not known if any neural crest cell is a true stem cell
I) Neural Crest Migration
A) Around time of tube closure cells migrate laterally and ventrally from dorsal side of tube
B) Starting position (anterior-posterior) specifies fate choice; experience on path determines
end result
C) Hox genes and neighboring cells in specification
D) Path neural crest cell takes depends on extracellular matrix
II) Cranial Nueral Crest
A) Cranial crest cells migrate through pharyngeal arches to form jaw cartilage
B) Cranial crest cells coordinate face and brain growth and tooth formation
III)
A)
B)
C)
Cardiac Neural Crest
Crest cells become portions of other neck structures
Crest cells contribute to formation of septum
Crest cells express transcription factor Pax3
IV) Cranial Placodes
A) Transient thickenings of the ectoderm in the head and neck
B) Forms sensory neurons
V) Trunk Neural Crest
A) Cells migrate through the anterior portion of sclerotome, but not posterior
B) Two paths: ventrally through anterior of sclerotome or dorsalateral between epidermis
and dermis
C) Semaphorin and ephrin proteins in posterior portion prevents cell migration
VI) Neuronal Specification and Axonal Specificity
A) 100 billion neurons in adult. 300 born
B) must make the right synapse to survive
C) Goodman and Doe’s list of 8 stages of neurogenesis
VII) Pattern Generation in the Nervous System
A) Pathway Selection
1) Axons travel along a particular route
(i) Guided by cell adhesion, proteins, and attraction/repulsion signals
2) Some proteins provide substrates allowing migrating of neurons while other proteins
block migration
(i) Ephrins and semaphorins can collapse growth cones. A way by which neurons
are kept on the right path to specific targets.
B) Some growth cones are attracted by very specific molecules that guide them to specific
targets
C) Synapse formation
1) Reciprocal induction and synaptic transmission
D) About 2/3 nuerons die. Apoptosis.
E) Neurotropic factors block apoptosis
F) Neural plasticity
1) behaviors present before birth
2) synaptic connections can be altered through life though less with age