TOPIC E: Dev Biology Flashcards
What are descriptive studies
Looking at expression patterns of mRNAs, non coding RNAs and proteins, fate mapping
What are manipulative studies
Altering a system and observing the effects, gene knockout, transplantation, adding a drug
What is fate mapping
Based on lineage tracing where a labelling group is added to cells of an embryo to see what they become in adult tissue.
Invertebrates animal model
Fly and round worm
ADV
Easy to keep and modify, rapid life cycle
DIS
Largely differing anatomy to humans
Lower vertebrates animal model
Zebrafish and clawed frog
ADV
easy to keep and manipulate, can add factors to environment (water)
DIS
Distant from humans
Higher vertebrate animal model chicken
Chicken
ADV
not in utero easy to manipulate
DIS
Longer life cycle
Higher vertebrate animal model mouse
Mouse
ADV
same organs and diseases as humans, easy to maintain
DIS
Embryos in utero, can be expensive, some phenotypes differ to human
What is an epithelial mesenchymal transition
Where an epithelial cell becomes a mesenchymal cell to enhance development
Less polarised
Motile not attached to other cells or membrane
Lie within matrix
what is cell fate
Developmental destination of a cell if left undisturbed in the embryo
What is specification and determination of cell fate
Specification: Cell fate is biased but can still be reversed if manipulated
Determination: Specified to form a specific cell type irreversibly, will differentiate autonomously if placed in different region
What is cell fate restriction governed by
Cells genome (gene expression)
Cells history (factors it has been exposed to)
Interaction with neighbours
What is pattern formation
The developmental process where cells acquire different identities depending on their relative spatial positions in the embryo
What are the steps of pattern formation
Cell proliferation Cell migration Changes in cell shape and size Cell differentiation Cell interaction (other cells and ECM) Apoptosis
What is pattern formation influenced by
Differential gene expression
Signalling between cells
How does differential gene expression influence pattern formation
Interaction between transcription factors inside cells and signalling molecules from neighbouring cells cause differential gene expression
Changes in cell behaviour
What are the regulatory elements and transcription factors controlling differential gene expression
Promoters: initiate gene expression
Enhancers: Bind activating factors
Inhibitors: bind inhibitory factors
Transcription factors bind to regulatory elements and play a role in gene expression
Explain what the HOX gene cluster is
Homeobox DNA sequence is found within genes involved in anatomical development and morphogenesis
Homeobox genes clustered together are called HOX genes
4 hox clusters (abcd)
Collinear with position along chromosome
What is a homeotic transformation
Where a body part develops as a different body part due to mutation of HOX genes
Sometimes the overlap of HOX genes prevents this from occurring in humans (known as functional redundancy)
How does signalling influence pattern formation
Induction is a change in cell fate due to signals sent from other cells. Limited repertoire used over and over.
What is lateral inhibition
Where cells send inhibitory signals to neighbouring cells to alter behaviour.
What are the 2 types of signalling cascades induction paracrine factors can cause
Protein kinase activity (FGF and TGF-beta)
Second messenger systems (Hedgehog and Wnt)
Outline fibroblast growth factor pathway
FGF activates Receptor tyrosine kinase MAPK pathway
on nucleus, activates transcription factors
Outline hedgehog pathway
Hedgehog binds to patched receptor which activates SMO to move into cilium so Gli is not broken down and transcriptional activation can occur
Outline Wnt pathway
Wnt binds to a frizzled receptor causing destruction complex to bind and be inhibited. beta-caterin can then act as a transcription factor
Outline transforming growth factor - beta pathway
TGF-beta binds to serine/threonine kinase receptor. Activates Smad proteins which target gene expression
What are morphogens
Secreted, diffusible molecule that can influence fat of a field of neighbouring cells via a concentration gradient
changes in dose changes the genes activated
What is morphogenesis
Organisation of form and shape of cells and tissues.
what factors affect morphogenesis
Direct cell-cell adhesion
Cell migration
How does direct cell-cell adhesion affect morphogenesis
Cells develop differential affinity to sort with similar cells
boundaries created by cell adhesion molecules
What are cadherins
Calcium dependent adhesion molecules
E-cadherins are on most early embryonic cells, and later in epithelial tissues.
N-cadherins are on neural cells
P-cadherins are on placental cells
How does cell migration affect morphogenesis
EMT causes morphogenesis by changes in characteristics
Change in polarity
Interaction with ECM
Motile force from actin and myosin
What are the major phases of embryonic development
Fertilisation Cleavage Blastocyst formation Implantation in uterus Gastrulation Neurulation Growth and organogenesis
What is regulative ability of an embryo
Regulation of production to ensure normal structures are formed
e.g. If some cells are removed, the embryo will ramp up production to remake the cells
Explain cleavage
Rapid cell division without size expansion
The individual cells are called blastomeres and undergo compaction
Tightly joined cells form the morula
Blastocyst forms with trophoblast and inner cell mass
What are the trophoblast and ICM
Trophoblast is the outer layer of cells which becomes the cyto- and syncytio- trophoblast and then part of the placenta.
The ICM becomes the epiblast and hypoblast which will later become the embryo and yolk sac
How are cells determined to become trophoblast or ICM
Inside outside hypothesis: Cells on inside become ICM and outside become trophoblast
Cell polarity model: If a cell divides parallel to zona pellucida it will become the trophoblast, if it divides perpendicular it becomes the ICM
What are the key transcription factors in the blastocyst
Oct4 for ICM formation, expression of pluripotency
Cdx2 for trophoblast formation
Nanog for epiblast formation
Gata6 for hypoblast formation
What is the gastrula
This is where the epiblast has become the 3 germ layers (a trilaminar disc)
What is the primitive streak
Ridge of cells along the axis of the embryo
its formation marks the start of gastrulation
What is the anterior visceral endoderm (AVE)
An extra embryonic tissue made of specialised cells in the hypoblast
Explain the starting signalling process of gastrulation
Together the primitive streak and AVE signal for gastrulation
BMP4 comes in and instructs cells of epiblast to make Wnt and Nodal.
AVE instructs epiblast to make Letty 1 and cerberus which restrict Wnt and Nodal to the posterior pole, causing the primitive streak.
At top of primitive streak is the node, which produces its own signals
Explain the movement of gastrulation through the primitive streak
Cells that pass through the node of the primitive streak will form part of the notochord, neural tube and head structures
Cells passing through the rest of the streak will produce the germ layers
Epiblast moves through, displacing hypoblast and first forming the endoderm and then the mesoderm, the remain epiblast cells become the ectoderm
What are the different types of potency
totipotent: make any cell type, zygote
pluripotent: most cell types, inner cell mass
multipotent: lineage restricted, germ layers
unipotent: one cell type e.g. neurons
Examples of tissues from each of the germ layers
Ectoderm: epidermis, CNS, neural crest cells
Mesoderm: Skeleton and muscles, dermis of skin
Endoderm: Epithelial lining of GI tract and associated organs and lining of respiratory, excretory and reproductive tract
Where do the 4 main tissues of the body arise from
Epithelium (all)
CT (mesodermal)
muscle (mesodermal)
nerve (ectodermal)
Outline neurulation
Production of the notochord and neural tube
Outline sonic hedgehog role in neurulation
Induction of the neural tube is by sonic hedgehog (Shh) signalling from the underlying notochord. Induces neural plate to form and fold into the neural tube
What are the 3 types of stem cells
Embryonic stem cells: from ICM
Adult stem cells: from adult tissue
iPSC: induced pluripotent stem cells due to reprogramming
What characteristics are proof of stem cell ability
expresses cell type specific markers in vitro
behave as the desired cells in vivo
Can self renew
Where can ASC be found
bone marrow, skin, gut and brain
haematopoietic stem cell, multipotent, red and white blood cells
mesenchymal stem cell, multipotent
What factors are used to produce iPSC
Oct4: activates Nanog for pluripotency
C-Myc: opens chromatin accessible to Sox2, Oct4 and nanog
Klf4 prevents cell death
What are the 2 types of cloning
Reproductive cloning: making a duplicate animal
Therapeutic cloning: Disease therapy
What is somatic cell nuclear transfer (SCNT)
where the nucleus of an ovum replaced into a somatic cell. iPSC can skip this step
