Exam 3 Flashcards
Fates of ectoderm
Epidermis (surface), neural crest, and neural plate/tube
Epidermis
Surface ectoderm, high levels of BMP
Neural crest
Moderate levels of BMP, lead to parts of the peripheral nervous system
Neural plate/ tube
Low BMP levels and Sox transcription factor expressed, becomes CNS and retina
Neurulation
Process of forming neural tissues, through inhibition of BMPs at dorsal midline
Role of Sox transcription factors
Activating the genes that specify cells to be neural plate and inhibiting formation of epidermis and neural crest by inhibiting BMP
Modes of neurulation
Primary and secondary
Primary neurulation
Anterior neural tube formation, Cells around the neural plate signal the neural plate cells to proliferate, invaginate, and separate from the surface ectoderm to form a hollow tube
Secondary neurulation
Posterior tube formation, Neural tube arises from the clustering of mesenchymal cells that hollow to form a tube
Junctional neurulation
Combination of primary and secondary neurulation where the two ends meet, creates the transitional zone
Process of primary neurulation
Neural folds are formed by the edges of the neural plate thickening and moving upward. Thickening of the folds form the neural groove, involves 4 stages
Stages of neurulation
- Elongation and folding of the neural plate
- Formation of mediolateral hinge point
- Formation of dorsolateral hinge point
- Closure of the neural tube
Process of elongation and folding of neural plate
Cell divisions in the anterior-posterior direction
Mediolateral hinge points
Cells at the midline, anchored to the notochord so hinge is formed and neural groove forms at the midline, neural folds elevate
Dorsolateral hinge points
Two, induced by and anchored to surface (epidermal) ectoderm, pull neural folds to the midline (convergence) while the ectoderm pushes
Closure of neural tube
Neural folds meet and adhere to each other at the midline, closing the neural tube
Hinge point mechanisms
Actin and myosin complexes apically constrict, along with increased cell divisions, leading to hinge
what is involved in the separation of the neural tube from the epidermis
differential adhesion, Neural tube express N-cadherins and epidermis express E-cadherins, SHH, TGF-beta, and BMP inhibition
neural tube closure defects
spina bifida (failure to close the posterior neuropore, exencephaly), anencephaly (failure to close anterior neuropore)
Process of secondary neurulation
occurs in the most posterior region of embryo, mesenchymal cells are patterned through morphogen gradients, cells condense into medullary cord (EMT), cavitation occurs, and individual cords combine to make longer single tube along a-p axis
morphogen gradients that pattern secondary neurulation
ectoderm cells express Sox (neural) and mesoderm activate Tbx6 (paraxial tissue)
medullary cord
cells go through EMT and condense into this in secondary neurulation
cavitation
hollowing out of medullary cord to make lumens (hollow spaces)
anterior patterning of the CNS
three primary vesicles formed, prosencephalon (forebrain), mesencephalon (midbrain), and rhombencephalon (hindbrain), starts before posterior neural tube has completed closure
rhomobomeres
small blocks of tissue that promote neuron differentiation, produced by rhombencephalon
differential induction of dorsal-ventral axis of neural tube
ventral nt forms motor neurons, dorsal nt forms sensory neurons, middle nt forms interneurons, TGF-beta gradient forms roof plate (BMP, dorsalin, and activin), SHH gradient forms floor plate, and combination of both TGF-b and SHH determine type of neuron formed
notochord role in DV axis of neural tube
potent inducer of ventral identity
what determines neuron identity
concentration or length of exposure to morphogen
contribution of neuromesodermal cells
in posterior, contribute to secondary neurulation, derived through FGF and Wbt maintained posterior epiblast, RA from anterior antagonizes FGF from posterior, some NMPs (neruomesoderm progenitors) are NT cell precursor, some become paraxial mesoderm
interaction of NMPs and signals
as NMPs leave tailbud, they interact with RA and become competent to respond to SHH and or BMPs, then they condense into neural tube with fates already determined. SHH responders become ventral, BMP responders become dorsal
placodes
derived through the thickening of non-neural ectoderm, sensory or non-sensory, formed and patterned through interactions with surrounding tissue
which placodes do not make sensory neurons
adenohypophyseal (pituitary) and lens
which signaling pathways induce cranial placodes
Wnt, BMP, FGF, SHH, and RA (retinoic acid), Wnt and BMP inhibited by FGF and cerberus
A-P axis signaling of placodes
SHH and RA, lead to general Six and Eya expression, give pre-placode identity
otic-epibranchial placode
responsible for hearing and balance, form in posterior region of cranial placodes (PPA, posterial placodal area), FGF from mesoderm induce PPA and are reinforced by neural plate
role of notch in otic placode
potentiates Wnt
Pharyngeal endoderm role otic-epibranchial placode
release BMPs, that induce epibranchial
otic pit
formed through proliferation (from signaling) and invagination of the placode
otic cup
formed through basal expansion and then apical constriction
otic vesicle
formed through the fusion of otic cup, similar to neural tube closure
ganglia
sensory neurons formed through delamination, necessary for morphogenesis, and eventually form cochleovestibular ganglion (CVG)
Role of Neural crest cells in morphogenesis of ear placode
acts as a physical guide for epibranchial ganglia
otocyst
precursor to the inner ear, must be further patterend and go through morphogenesis, folds and extends to create vestibular and cochlear structures
organ of corti
ear receptor organ formed through a complex series of differentiation, contains hair cells (sense sound) and supportive/structural cells
Signal patterning of ear placode
A-p axis patterned by retinoic acid (RA), d-v axis by SHH and Wnt, and Medial-lateral access by Wnt and FGF
Eye components
retina and retinal epithelium (neural) and non-neural lens placode
lens placode
formed through reciprocal interactions between the optic vesicle and itself
Anterior placode bias
bias to form lens, which triggers Pax6. Neural crest cells inhibit lens fate, but never contact lens due to the optic cup, which allows it to stay lens
movements of eye placode morphogenesis
apical constriction, basal constriction, and filapodial contact (anchors lens to optic vesicle to allow for inductive signaling)
optic cup layers
outer layer is non-nerual crest derived epithelium, inner contains retina, photoreceptors, and neurons that combine to create optic nerve, lens placode on outside of optic cup
interaction of which structures forms the eye
lens placode and optic cup
Signaling of lens placode (early gastrulation)
complex inductive events involving Noggin, Otx2, ET, Rx1, and Pax6. Starting in gastrulation, Noggin inhibits BMP and ET(first eye field gene) transcription factors, allowing for the expression of Otx2. Otx2 induces ET. Differential expression of Otx2 across the DV axis of the forebrain leads to a differential repression of Noggins ability to inhibit ET, allowing for ET and eye field (patterning done by neurulation)
SHH role in eye development
inhibits Pax6 along the midline, separating the eye field into left and right
is optic vesicle sufficient to produce lens?
no! lens and retina development require reciprocal signaling (FGFs, Wnt, and BMPs)
signaling of lens placode (late gastrulation)
BMP and Wnt inhibitors and FGFs induce ectoderm to be come competent to form lens. neural tissue forms optic vesicle which grows and contacts lens placode, optic vesicle cells produce BMP, FGF, and delta (notch pathway) to instruct the cells to become lens placodes. Lens placode cells secrete FGFs that induce retina formation. Optic vesicle becomes optic cup and surrounds lens placode, which induces the differentiation of lens cells
epidermis
skin, derived from the non-neural ectoderm and promoted by BMP signaling, largest singular organ, creates an impenetrable barrier around entire organism, and regenerative
parts of the epidermis
dermal layers, hair follicles/feathers, and sebaceous(oil) and sweat glands
role of BMPs in epidermis formation
block neural pathway with transcription factors and promote epidermis specification
2 layers of epidermis
come from one layer, periderm (temporary) is outer layer, basal layer/stratum germinativum is the inner layer.
basal layer
contains stem cells anchored to basal lamina
what regulates cell divisions of the epidermis
dermis signaling pathways, FGFs anf TGFs. As cells divide notch signaling is activated (includes jagged ligand)
notch signaling in epidermis leads to
older cells being pushed outwards, redicing proliferation, and inducing keratin expression, which leads to keratinocytes
keratinocytes
differentiated epidermal cells that are bound tightly together and form the stratum corneum. They also stop transcription and metabolic activity
when does epidermal development begin
after neural tube closure
ectodermal appendages
structures formed on the epidermis like hair or feathers formed through interaction of the mesenchymal dermis and ectodermal epidermal layers, which forms epidermal placodes
movement of ectodermal placodes relative to mesenchyme
in all cases, ectodermal placodes invaginate inwards towards mesenchyme cells
inductive abilities of dermal mesenchyme
will induce formation of whichever appendage it forms in other types of epidermis
signaling pathways involved in tooth formation
FGFs, Wnts, Shh, BMPs, and TGFs. BMP4 inhibits tooth ability, FGF8 promotes tooth ability
enamel knot
signaling center of tooth, once formed it may use multiple signals to pattern surrounding tissue
Role of Wnt/B-catenin
critical for establishing placodes for epidermal appendages
role of FGFs in epidermal appendages
regulate migration of mesenchyme to form condensate (condensed mesenchyme) like enamel knot
FGFs and their appendage
FGF8 is dental, FGF20 are hair follicles, and FGF10 are mammary glands. Loss of each results in loss or reduction of traits
What patterns field and structure of appendages
other signaling interactions that limit boundaries, shape, cell identities
appendages that contain stem cells to regenerate
teeth (except mammals), hair, skin, mammary
mammary stem cell developmental events
initial development, puberty, and pregnancy
ability of stem cells
to differentiate into all necessary cell types
hair stem cells
follicle forms as other placodes with the invagination of epidermal layers and communication between dermal and epidermal layers, contains three stem cell types
3 hair stem cell populations
hair shaft, sebaceous gland, and germinal layer of epidermis (keratinocytes). There is evidence that each type can be converted to others when needed for healing
cycles of hair growth/regeneration
anagen is growth, telogen is rest, and catagen is regression
what determines hair lengths
time spent in anagen (growth) stage
region responsible for regeneration of hair
bulge region
stem cell populations of bulge region
HFSC (hair shaft and sheath) and melanocytes (pigment)
signaling of hair cycles
to activate growth, fibroblasts use Wnt and dermal papilla use FGFs and BMP inhibitors. for telogen/catagen stages, adipocytes and fibroblasts use BMPs
HFSC bulge cell types
outer and inner, inner is progeny of outer and represses outer proliferation using BMP and FGFs
hair shaft formation
occurs during anagen by growing around dermal papilla to form the root sheath
Neural Crest Cells
ectoderm derived, vertebrate specific cells along the dorsal side of the Neural tube that eventually lead to PNS, endocrine systems, and connective tissues
transience of neural crest cells
once cells migrate, neural crest disappears as the cells become their specialized forms. No adult population of NCCs
types of nerual crest cells
Cranial NC (anterior), cardiac NC (ear to 3rd somite), trunk NC, and vagal NC
Cranial NC
become face structures like cartilage, bones, and neurons as well as pharyngeal structures like thymus, teeth, ear and jaw bones
cardiac NC
become melanocytes, neurons, connective tissues, cartilage, smooth muscle and connective tissues of the aorta
trunk NC
Ventral become sensory neurons of the dorsal root ganglia, adrenal and aortic nerves. Dorsal become melanocytes
potency of NCCs
multipotent, can generate different cell types with restricted specificity due to location of cells
Equivalence of trunk and cranial NCCs
not equivalent, can both generate neurons, melanocytes, and glia but trunk NCCs cannot form bone/skeleton due to the expression of Hox genes in the trunk region
evolution of trunk NCCs
Hox expression has led to the loss of skeletal ability, no hox expression in cranial NC so skeletal ability is present
role of Hox gene expression in NCCs
give regionally limited identity
fates of NCCs come from
interactions with different environments along migratory journey, receive different signaling patterns that specify cell fates
Main signals of Neural crest cell fates/migration
Wnt and BMPs, FGFs, TGF-beta, and Fox and Sox
Gene regulatory network general structure
Wnt, BMPs, and TGF-betas induce Msx1, Gbx2, and other ectodermal signals. Msx1 and Gbx2 induce Pax3/7 and dlx5/6, which are neural plate border specifiers and give border cells the ability to form both NCCs and dorsal NT cells. Pax3/7 and dlx5/6 induce neural crest specifiers FoxD3, Sox 9, and Snail (pre-migratory) as well as the migratory Sox10
EMT
cells transitioning from epithelial to mesenchymal through downregulation of cadherins. BMPs activate Wnt genes, which allow for delamination due to expression of Snail2 and Foxd3
cadherin groups
N-cadherins (NT), E-cadherins (ectoderm), and Cadherin6B (pre-migratory NC)
Signals of NCC migration
BMP induces Wnt, Wnt induces Rac1 and RhoA, which lead to delamination event
Rac and RhoA activity during EMT
increased RhoA and apical constriction along with activation of Rac on basal side, Rac regulate cytoskeleton producers filopodia and lamellipodia (responsible for migration), RhoA keeps Snail and Foxd active as well as organizing actin for migration
Where do delaminating NCCs leave from the NT
basal surface, degradation of ECM around basal surface
contact inhibition
mechanism in which when NCCs come in contact with each other, they stop and redirect movement, pushing opposite of the point of contact. This makes sure that NCCs maintain their identities and do not cross paths, which would result in them receiving different signals and differentiating into different cells than intended. Only occurs when NCCs touch each other, not when they touch other cells
morphogenetic trigger for EMT
convergent extension during gastrulation is the first cue, as cells compress, they create a stiff structure for NCCs to migrate along
role of Snail2 in EMT
repressive, limits boundaries of cadherins so that each type of cell can express specific ones (E,N and Cadherin6B)
collective cell migration
migratory pattern in which leading edge cells pull the cells behind, which activate their cytoskeleton
role of non-cannonical Wnt/PCP pathway in NCC migration
regulates intracellular actin cytoskeleton activity (RhoA and actin disassembly
requirements for collective cell migration
cell-cell adhesion within the cluster, after leaving the NT, NCCs express N-cadherin to maintain grouping, contact inhibition keeps cells directional, and chemoattractant C3a secreted by NCCs keep group together
