Body plan (part 3) Flashcards
What structures does the ectoderm develop into
epidermis, CNS and neural crest
What does the endoderm develop into
GI tract and the liver
What structures does the mesoderm develop into
blood, bone, muscle kidney and the gonad
What does the animal cap ectoderm have bipotency for
epidermal cells or neural ectoderm
How is epidermal or neural ectodermal lineage determined
by signals from the mesodermal notochord, prechordal plate and anterior endoderm
What are the stages of neurulation
- ectodermal cells overlying the notochord become transformed into the neural plate
- ectoderm on either side of the notochord thickens to form neural folds
- neural folds invaginate into the interior of the embryo, rolling up the neural plate to become the neural tube
What stages of development do different species begin developing differently
late stages, when class and species specific features are established
What is neural induction
when ectodermal cells become specialised to become the neural progenitor cells that constitute the neural plate
Where do the neural-inducing signals come from
the organiser, just before gastrulation
Where do neural inducing signals come from after gastrulation
from the extending notochord and prechordal plate
What are BMPs
a member of TBG beta family that repress neural differentiation. act as autocrine signals that induce differentiation of the ectoderm into epidermis
What happens to ectodermal cells in the absence of BMP
differentiate into neural cells
What do the organiser, notochord and prechordal plate secrete and why?
proteins such as chordin, noggin, follistatin, cerberus and Xnr3 that inhibit B,P signalling and result in neural specification of ectodermal cells
How do BMPs work
activate via membrane cell receptors with serine/threonine kinase activity. regulated by kinase phosphorylation. when phosphorylated = active and genes are trancribed. activates SMAD transcription factors
What does the neural tube along the anteroposterior axis divide into?
Forebrain, midbrain, hindbrain and spinal cord regions
What does the spinal cord divide into along the dorsoventral axis?
Roof plate, dorsal and ventral interneurons, motor neurons, floor plate Abscence
The neural tube becomes patterned after neuralation along the anteroposterior axis, how?
Gradients of Wnts, FGFs and retinoic acid
What does the posterior neural tube differentiate into?
The spinal cord
How many progenitor domains are there? How do the domains become divided?
Neural progenitors receive signals to subdivide the neural tube into 11 progenitor domains
What are the 11 progenitor domains?
6 Dorsal interneurons subtypes (D1-D6), 4 ventral interneurons subtypes (VO-V3) and all spinal motor neurons (MN).
How are ventral cell types generated in the posterior neural tube?
If the notochord is removed, the floor plate (FP) , motor neurons (MN) and most ventral interneurons do not form. Notochord produces signals that induce formation fo the floor plate and ventral neuronal cell types
What is Shh?
A vertebrate homologoue of the hedgehog gene of drosophila. It is expressed in many regions associated with developmental signalling including the notochord and floor plate.
Autocleaves into N and C terminal
At a low concentration of Shh-N are dorsal or ventral interneurons made?
Dorsal
At high concentrations of Shh-N are more dorsal or ventral interneurons formed?
Ventral
What does the knockout of Shh in transgenic mice lead to?
The Abscence of floor plate
Abscence of motor neurons and most ventral interneurons
What is Shh-N produced by?
Notochord and floor plate
What is organogenesis
transforming an amorphous mass of cells into a complete organ
How do adherens junctions form
due to interactions between cadherin proteins
How is the cytoplasmic portion of the cadherin protein linked to the actin cytoskeleton
via catenins which form like-with-like interactions
How are different cell types sorted
based on their different adhesive properties
What causes different adhesive properties between cell types
different expression of cell adhesion molecules such as E-cadherin and adherens junctions
What specifies the mesoderm and endoderm in veretebrates
nodal
What determines the subdivision of the endoderm in different organ primordia
TF code
What is liver zonation
hepatocytes around the central vein differ from those around the portal vein = hepatocyte heterogeneity which allows different gene expression and different metabolic functions despite their morphology being the same
How is the liver bud developed
through the EMT transition of hepatoblasts
What does a high concentration of nodal/activin signalling specify?
the mesoderm and endoderm
What does FGF and BMP specify?
hepatoblasts - liver cell precursors
Describe the stages of how liver bud cells can be induced from pluripotent stem cells
Embryonic stem cell treated with activin to develop mesoderm and endoderm
further high expression of activin creates the definitive endoderm
expression of FGF and BMP produces hepatoblasts
expression of HGF, Dex and OSM produces hepatocytes
What is an organoid
collection of organ-specific cell types that develop from stem cells of organ progenitors and self-organises through cell sorting and spatially restricted lineage management
What stages turn a differentiating pluripotent stem cell into an organoid
cell sorting and lineage commitment
How can vascularised functional human liver organoids be made in the lab?
using iPSC-derived hepatocytes and growing them in a culture with HUVECs (human umbilical vein endothelial cells) and MSCs (mesenchymal stem cells). this allows the organoids to grow extensive vascular trees
What is a weakness of using iPSC/ESC derived hepatocytes?
they are immature cells so have partial functionality
How can we apply knowledge regarding developmental stem cells
in disease modelling
drug safety and efficacy testing
organ replacement therapy
liver organoids for toxicology screens
bio banking of organoid cultures
research on disease and genetics
