Lecture 4: Mechanism of Differentiation Flashcards
Specification of a Cell Fate
The process by which a single zygote develops into a multicellular organism composed of specialized, differentiated cells.
Cell Differentiation
Specification of a Cell Fate
What are the key body axes in vertebrate development? (2)
- Antero-Posterior Axis (Head to Tail)
- Dorso-Ventral Axis (Back to Belly)
Specification of a Cell Fate
Cells differentiate at the cellular level through __, where specific genes are turned on or off to guide cell specialization.
gene expression regulation
Specification of a Cell Fate
How do cells recognize positional information for differentiation? (3)
- **Morphogen Gradients **– Signaling molecules create concentration differences that guide cell fate.
- **Cell-to-Cell Communication **– Signaling pathways like Notch, Wnt, and Hedgehog.
- Polarity Proteins – Intracellular proteins that help establish cell orientation.
Specification of a Cell Fate
What are the three stages of cell commitment? (3)
- Specification – The cell differentiates autonomously in a neutral environment but remains reversible.
- Determination– The cell’s fate is fixed and cannot change, even if relocated.
- Differentiation– The final stage, where the cell becomes fully specialized.
Specification of a Cell Fate
Before a cell fully differentiates, it undergoes a __ process, which determines its fate. This process involves changes in cellular biochemistry and function.
commitment
Specification of a Cell Fate
- The cell can differentiate autonomously in a neutral environment (without external signals).
- The fate of the cell is specified but still reversible.
stages of cell commitment
Specification
Specification of a Cell Fate
- The cell will differentiate autonomously even if moved to a different region of the embryo.
- The fate of the cell is irreversible or fixed.
stages of cell commitment
Determination
Specification of a Cell Fate
The final stage where the cell fully generates into a specialized cell type with specific functions.
stages of cell commitment
Differentiation
Specification of a cell fate
What are the three (3) strategies of specification?
- Autonomous Specification
- Conditional Specification
- Syncytial Specification
Specification of a cell fate
A developmental strategy where cells inherit morphogenetic determinants (e.g., transcription factors, mRNAs) that direct their fate independently of neighboring cells.
strategies of specification
autonomous specification
Specification of a cell fate
- Blastomere inherits a set of transcription from the __.
- Regulation of Gene Expression: These transcription factors regulate __, directing the cell into a particular path of development.
- Different regions of the egg contain different __ (transcription factors or their mRNAs) that influence the cell’s development.
- Cell Fate is __: The cell “knows” what it is to become very early and without interacting with other cells.
strategies of specification: autonomous specification
- egg cytoplasm
- gene expression
- morphogenetic determinants
- Pre-Determined
Specification of a cell fate
- Trochoblast differentiation in Patella
- At the 16-cell stage, specific blastomeres are already committed to forming ciliated trochoblast cells.
- Even when removed and cultured separately, these cells still form cilia.
- Demonstrates that cell fate is intrinsically determined.
What type of strategy in specification is this?
autonomous specification
in snails
Trochoblast differentiation in Patella
is the classic experiment by Wilson (1904) demonstrated autonomous specification, showing that trochoblast cells contain all the necessary instructions for their development from the early cleavage stages.
Specification of a cell fate
- B4.1 blastomeres → Tail muscle formation
- Contains yellow-pigmented cytoplasm with Macho mRNA, which codes for a muscle-specific transcription factor.
- Transferring this cytoplasm into other cells results in muscle formation.
- Removing these cells prevents muscle formation.
What type of strategy in specification is this?
autonomous specification
This experiment demonstrated that tunicate cells inherit developmental instructions from the egg cytoplasm, meaning their fate is intrinsically determined rather than relying on external cues. This is a classic example of autonomous specification in embryonic development (Reverberi and Minganti, 1946).
Specification of a Cell Fate
- Ability of cells to achieve their respective fates by interacting with other cells.
- What a cell becomes is largely specified by paracrine factors secreted by its neighbors.
strategies of specification
Conditional Specification
Specification of a Cell Fate
- Cells rely on paracrine signals from neighbors to determine their fate.
- If a part of the embryo is removed, the remaining cells can compensate and adjust.
What type of specification strategy is this?
Conditional Specification
Specification of a Cell Fate
- First testable model of cell specification, proposed by August Weismann in 1888.
- Proposed that each cell of the embryo would develop autonomously.
- Stated that sperm and egg provide equal chromosomal contributions (both quantitatively and qualitatively) to the new organism.
Germ Plasm Theory
Specification of a Cell Fate
Who proposed the Germ Plasm Theory?
August Weismann (1888)
Specification of a Cell Fate
What did the Germ Plasm Theory propose? (3)
- The embryo develops autonomously based on inherited determinants.
- Germ cells carry all inherited information and give rise to both germ and somatic cells.
- Somatic cells receive only a subset of these determinants and cannot pass genetic information to offspring.
Specification of a Cell Fate
What did Weismann’s theory reject?
Lamarckian inheritance, which suggested that acquired traits could be inherited.
Specification of a Cell Fate
Why is the Germ Plasm Theory important? (2)
- Laid the foundation for modern genetics.
- Established the concept that only mutations in germ cells are inheritable.
Specification of a cell fate
Experiment on cell specification:
__(scientist) used a hot needle to kill one of the cells in a __(specimen). The result was that ______ of a larva developed. The conclusion was that specification was __, meaning all instructions for development were present inside each cell.
specification strategy
- Wilhelm Roux
- 2-cell frog embryo
- only the right or left half
- autonomous
Specification on Cell fate
Experiment on Cell Specification:
__(scientist) conducted isolation experiments where each blastomere from a 2-cell embryo formed a complete larva. Each isolated blastomere regulated its development to produce a complete organism, providing strong evidence that a cell’s fate is determined by interactions with __ rather than __.
What strategy of specification was showed?
- Hans Driesch
- neighboring cells
- intrinsic cytoplasmic factors
Conditional Specification
Specification on a cell fate
Hans Driesch separated the 4 blastomeres of a sea urchin embryo. When the 4 blastomeres were separated, each individual cell was still capable of forming a smaller but complete __ on its own. The resulting larvae were __, indicating that while each isolated blastomere could form all necessary cell types, variations still occurred due to differences in __.
What specification strategy does this prove?
- pluteus larva
- not identical
- early cell interactions
Conditional specification
Specification on a cell fate
Recombination Experiment:
__(scientist) applied gentle pressure to alter cleavage patterns, reshuffling the __ and changing their expected positions within the developing embryo.
Contrary to __’s predictions, the embryos developed into __, demonstrating that early embryonic nuclei are __ and that cell fate is determined by __ information within the __, not by a fixed set of __.
specification strategy
- Hans Driesch
- nuclei
- Weismann
- normal larvae
- equivalent
- positional
- embryo
- nuclear determinants
Specification on a cell fate
How did Hans Driesch’s work provide crucial evidence against autonomous specification and support conditional specification?
specification strategy
Driesch’s experiments showed that cell fate is influenced by interactions with neighboring cells rather than being predetermined. His findings highlighted the importance of cell-to-cell communication and the embryo’s ability to regulate development based on its environment.
Specification on a cell fate
A __ is a cytoplasm that contains many nuclei. __ occurs when the specification of presumptive cells happens within such a __, predominating in most insect classes. Body regions are specified before __ of the blastoderm through __, and variable cleavage leads to no rigid cell fates for particular nuclei.
specification strategy
- syncytium
- Syncytial specification
- syncytium
- cellularization
- cytoplasmic interactions
Specification on a cell fate
What happens after cellularization in syncytial specification, and how does it relate to autonomous and conditional specification?
A: After cellularization, both autonomous and conditional specification can be observed. Initially, positional information is determined by the distribution of __ in the shared __, but once individual cells form, their fate is influenced by both __ and _______________.
specification strategy
- morphogens
- cytoplasm
- intrinsic factors
- interactions with neighboring cells
Specification on a cell fate
How does syncytial specification occur in early Drosophila embryogenesis?
syncytial specification
In early Drosophila embryogenesis, nuclear divisions occur without cytokinesis, resulting in a syncytial blastoderm—a single cell with many nuclei sharing a common cytoplasm. Morphogen gradients form within this shared cytoplasm, instructing nuclei about their positions before cellular membranes develop, ensuring proper body patterning.
Specification on a cell fate
What is the function of Bicoid in Drosophila embryonic development, and how does it establish the anterior-posterior axis?
Bicoid is produced in the __ portion of the egg, forming a high concentration in the __ and gradually declining toward the __. It acts as a transcription factor that activates genes for __ and __ formation and inhibits __, preventing __ structures from forming in the __ region, thereby establishing the anterior-posterior axis.
syncytial specification
- anterior-most
- anterior
- posterior
- head and thorax
- Caudal
- posterior
- anterior
Specification on a cell fate
Q: What is the function of Caudal in Drosophila embryonic development, and how does it interact with Bicoid?
A: Caudal is produced in the __ portion of the egg, forming a ___. It is important for the development of __ and __ structures. Bicoid suppresses Caudal in the __, ensuring proper regional development by preventing __ structures from forming in the __ region.
syncytial specification
- posterior-most
- posterior-to-anterior gradient
- abdominal and posterior
- anterior
- posterior
- head
Specification on a cell fate
Q: How do the opposing gradients of Bicoid and Caudal contribute to the body patterning of the Drosophila embryo?
A: The opposing gradients establish the __, instructing __ about their future roles before __ form. __ is high in the anterior and low in the posterior, while __ is high in the posterior and low in the anterior. This ensures that positional information is correctly distributed before __, guiding proper body patterning.
syncytial specification
- anterior-posterior axis
- nuclei
- cellular membranes
- Bicoid
- Caudal
- cellularization
Specification on a cell fate
Specification of the Germ Layers:
* Animal hemisphere blastomeres → become __ (__ and __).
* Vegetal hemisphere cells → become __ (__ and __).
* __ → Forms from the internal cytoplasm around the equator.
* __ → Established in the embryo by the vegetal cells.
Progressive Determination of the Amphibian Axes
- Ectoderm (skin and nerves)
- Endoderm (gut and associated organs)
- Mesodermal cells
- General fate map
Specification on a cell fate
Specification of the Germ Layers:
The general fate map is established in the __ by the __, which differentiate into the __ and induce the cells above them to become __.
Progressive Determination of the Amphibian Axes
- embryo
- vegetal cells
- endoderm
- mesoderm
Specification on a cell fate
What are the two major functions of vegetal cells in amphibian development? (2)
Progressive Determination of the Amphibian Axes
- differentiate into endoderm
- induce the cells immediately above them to become mesoderm.
Specification on a cell fate
__ is a transcription factor tethered to the vegetal cortex, involved in the “bottom-up” specification of the frog embryo. It is critical for generating both the endodermal and mesodermal lineages by guiding early development through the formation of the endoderm and the induction of mesoderm formation.
Progressive Determination of the Amphibian Axes:
Amphibian embryonic development
VegT
Specification on a cell fate
If VegT transcripts are destroyed using __, the entire embryo becomes __, lacking __ and __ components, showing that VegT is essential for __.
Progressive Determination of the Amphibian Axes
Amphibian embryonic development
- antisense oligonucleotides
- epidermis
- mesodermal
- endodermal
- germ layer specification
Specification on a cell fate
a transcription factor that activates endodermal genes, ensuring that vegetal cells become endodermal cells.
Progressive Determination of the Amphibian Axes
Soxl7
Specification on a cell fate
are secreted from vegetal cells in the nascent endoderm and instruct the cells above them to become mesoderm by signaling them to express phosphorylated Smad2, which activates the Eomesodermin and Brachyury (Xbra) genes.
Progressive Determination of the Amphibian Axes
Nodal paracrine factors
Specification on a cell fate
Nodal paracrine factors are secreted from __ in the __ and instruct the cells above them to become __ by signaling them to express phosphorylated __, which activates the __ and __ genes.
Progressive Determination of the Amphibian Axes
- vegetal cells
- nascent endoderm
- mesoderm
- Smad2
- Eomesodermin and Brachyury (Xbra)
Specification on a cell fate
The __ involves Eomesodermin and Smad2 proteins activating zygotic VegT genes, which sustain mesoderm development by reinforcing VegT expression.
Progressive Determination of the Amphibian Axes
positive feedforward loop
Specification on a cell fate
Specification of Germ layers:
In the __ stage, the fundamental germ layers become specified: __ become endoderm (__), __ become mesoderm (__), and __ (not yet receiving signals) become ectoderm.
Progressive Determination of the Amphibian Axes
- late blastula
- vegetal cells
- Soxl7
- equatorial cells
- Eomesodermin
- animal cap cells
Specification on a cell fate
Specification of mesoderm in amphibian embryos:
The __ region of the __ accumulates __ for __ and, in the future __ region, mRNA for the __.
At the __ stage, __ is translated, inducing the future ___ to transcribe genes for Wnt antagonists such as Dickkopf.
Progressive Determination of the Amphibian Axes
- vegetal
- oocyte
- mRNA
- VegT
- dorsal
- Nodal paracrine factor Vg1
- late blastula
- Vg1 mRNA
- dorsal mesoderm
Specification on a cell fate
Specification of mesoderm in amphibian embryos (late blastula stage):
VegT mRNA is translated, activating nuclear genes encoding __, which belong to the __ family. These activate the expression of the transcription factor __ in the presumptive mesoderm.
Progressive Determination of the Amphibian Axes
- Nodal proteins
- TGF-β
- Eomesodermin
Specification on a cell fate
Specification of mesoderm in amphibian embryos:
Eomesodermin, along with activated Smad2 from Nodal proteins, further activates __ encoding __, shifting its expression from maternal mRNAs in the presumptive __ to nuclear expression in the presumptive __.
Progressive Determination of the Amphibian Axes
- nuclear genes
- VegT
- endoderm
- mesoderm
Specification on a cell fate
a group of cells in the dorsal lip of the blastopore in amphibian embryos that induces the development of the central nervous system and other dorsal structures, introducing the concept of embryonic induction.
Determination of Embryonic Axes
Spemann’s Organizer
Specification on a cell fate
a cluster of dorsal vegetal cells in a blastula that serves as a primary inducing region, playing a crucial role in amphibian development by inducing the Spemann-Mangold organizer, which forms the body axis.
Determination of Embryonic Axes
Nieuwkoop Center
Specification on a cell fate
refers to the phenomenon where different areas or regions of an organism, tissue, or system exhibit distinct characteristics and functions, enabling them to perform specialized tasks during development.
Determination of Embryonic Axes
Regional Specificity
Specification on a cell fate
What are the axes? (3)
Determination of Embryonic Axes
- Dorso-Ventral Axis
- Antero-Posterior Axis
- Left-Right Axis
Specification on a cell fate
In Xenopus and other amphibians, anterior-posterior axis formation is linked to the formation of the dorsal-ventral axis. The process begins at __, where the __ entry point causes a __, moving the transcription factor __ to the side __ the __ entry point.
Determination of Embryonic Axes
- fertilization
- sperm
- cytoplasmic shift
- β-catenin
- opposite
- sperm
Specification on a cell fate
How does β-catenin determine the dorsal side of the amphibian embryo?
Determination of Embryonic Axes
When the sperm enters the egg, it causes a shift in the cytoplasm, moving β-catenin to the region opposite the sperm entry point. The accumulation of β-catenin in this region specifies the dorsal side of the embryo.
Specification on a cell fate
__ induces the expression of genes that help form the Spemann organizer, which directs __ movement during __. This movement establishes the __ by guiding the __.
Determination of Embryonic Axes
- β-catenin
- mesodermal
- gastrulation
- anterior-posterior axis
- mesodermal involution
Specification on a cell fate
How does mesoderm movement contribute to the establishment of the body plan in amphibian embryos?
Determination of Embryonic Axes
- The mesoderm starts moving inward (involution), shaping the embryo.
- This movement lays out the body plan, forming structures from head (anterior) to tail (posterior), ensuring proper axis formation.
Primary Embryonic Induction
The process by which the __ forms through interactions with the underlying __ is called primary embryonic induction. This mechanism helps organize the __.
Definition of Primary Embryonic Induction:
- Central nervous system (CNS)
- Mesoderm
- vertebrate body
Primary Embryonic Induction
The first mesodermal cells that migrate over the __ induce the ectoderm to form anterior structures such as the __. Mesoderm that involutes later signals the ectoderm to form more __ structures, including the __ and __.
Organizer and Its Role:
- Dorsal blastopore lip
- Forebrain
- Posterior
- Hindbrain
- Spinal cord
Primary Embryonic Induction
The scientist __, along with __, conducted research at the University of Freiburg, Germany. In 1935, he was awarded the Nobel Prize for his work on __.
- Hans Spemann
- Hilde Mangold
- Embryonic induction
Primary Embryonic Induction
In an experiment using __ embryos, Spemann used a __ to constrict the fertilized egg, keeping the __ on one side. The nucleated side continued cleavage, while the other remained undivided. When a __ entered the undivided side at the 16-cell stage, and the ligature was tightened, each half developed into a normal embryo. This demonstrated that early blastomere nuclei are __.
Spemann’s Experiment on Nuclear Equivalence
- Newt (Triturus taeniatus)
- Ligature
- Nucleus
- Single nucleus
- Totipotent
Primary Embryonic Induction
In Spemann’s experiment, when the egg was divided along the plane of the first __, each blastomere received half of the __ and developed into normal embryos. However, if only one blastomere received the entire __, it alone developed normally, while the other produced a mass of __ tissue.
Spemann’s Experiment on Dorsal-Ventral Axis Formation
- Cleavage
- Gray crescent
- Gray crescent
- Unorganized
Primary Embryonic Induction
The __ contains essential developmental signals for forming dorsal structures. If one half of the embryo lacks this region, it fails to develop key structures such as the __, __, and __.
Spemann’s Experiment on Nuclear Equivalence
- Gray crescent
- Nervous system
- Notochord
- Somites
Primary Embryonic Induction
In Spemann’s experiment, the dorsal side of the embryo developed into a __________, while the ventral side formed an unorganized tissue mass called the __________. The malformed tissue contained __________, __________, and __________ cells but lacked key dorsal structures.
Findings on Dorsal-Ventral Development
- Normal larva
- Bauchstück
- Epidermal (ectoderm)
- Blood and mesenchyme (mesoderm)
- Gut (endoderm)
Primary Embryonic Induction
When the egg was divided perpendicular to the first __________, some cytoplasmic __________ were not equally distributed. These are essential for proper embryonic __________.
Unequal Cytoplasmic Distribution
- Cleavage plane
- Determinants
- Axis formation
Primary Embryonic Induction
After fertilization, cytoplasmic __ occur within the egg, exposing the __, a region of cytoplasm opposite the sperm entry point. This region is critical for initiating __ formation.
Cytoplasmic Movements After Fertilization
- Rearrangements
- Gray crescent
- Dorsal structure
Primary Embryonic Induction
Cytoplasmic reorganization, driven by the __________, involves the movement and rearrangement of cellular components such as __________ and __________. These changes are essential for processes like cell __________, __________, and __________.
- Cytoskeleton
- Organelles
- Structures
- Division
- Migration
- Development
Primary Embryonic Induction
In a fertilized egg, __ (~90° rotation) redistributes maternal determinants, helping establish the __ axis. This movement is guided by __, which also direct pronuclear migration.
- Cortical rotation
- Dorsal-ventral
- Microtubules
Primary Embryonic Induction
At the two-cell stage, the __ distribution of cytoplasmic determinants plays a role in cell fate determination. The __ and __ cytoskeleton help maintain cell polarity.
Cytoplasmic Rearrangement at the Two-Cell Stage
- Asymmetric
- Actin
- Microtubule
Primary Embryonic Induction
During the mid-blastula stage, cytoplasmic distribution becomes more __________. The Mid-Blastula Transition (MBT) introduces __________ cell cycles and initiates __________ gene activation.
Mid-Blastula Transition (MBT)
- Even
- Longer
- Zygotic
Primary Embryonic Induction
The early gastrula stage involves major cytoplasmic reorganization due to gastrulation movements such as __ and __. These changes allow __ to migrate and form the three __.
Cytoplasmic Reorganization in Gastrulation
- Invagination
- Involution
- Cells
- germ layers
Primary Embryonic Induction
Spemann’s experiment showed that the __ region was essential for embryonic development. Fate maps revealed that it gives rise to the __ of the blastopore, which later initiates __ and forms the __ and __.
- Gray crescent
- Dorsal lip
- Gastrulation
- Notochord
- Head mesoderm
Primary Embryonic Induction
Gastrulation is the process in which the __ reorganizes into a __, forming the three primary germ layers: __, __, and __.
Gastrulation and Germ Layer Formation
- Blastula
- Gastrula
- Ectoderm
- Mesoderm
- Endoderm
Primary Embryonic Induction
Spemann found that in early gastrulae, cells were __________, meaning their fate depended on __________. However, in late gastrulae, cells were __________, meaning their fate was already determined.
Spemann’s 1918 Experiment on Cell Fate
- Uncommitted
- Location
- Committed
Primary Embryonic Induction
The early newt gastrula exhibits __ development, meaning cell fate depends on its __. In contrast, the late gastrula exhibits __ development, where cells develop independently of their location.
- Conditional (regulative)
- Location
- Autonomous (mosaic)
Primary Embryonic Induction
When tissue from the __ of an early gastrula was transplanted to another region, it adapted and developed according to its __. This demonstrated that early-stage cells were still __ in their fate.
Early Gastrula Transplantation Results
- Dorsal lip
- New location
- Flexible (undetermined)
Primary Embryonic Induction
Spemann’s research led to the discovery of the __________, which proved that the __________ of the blastopore induces the formation of the __________ and establishes the body axis.
- Spemann-Mangold Organizer
- Dorsal lip
- Neural tube
Primary Embryonic Induction
The dorsal lip of the blastopore is derived from the __________ cytoplasm.
Origin of the Dorsal Lip
Gray crescent
Primary Embryonic Induction
When the dorsal lip is transplanted into another gastrula’s belly skin region,
* It continues as the __.
* It initiates __ and __ in the surrounding tissue.
* It induces the host cells to form a complete __.
* A __ is formed, conjoined face to face with the host.
- dorsal blastopore lip
- gastrulation and embryogenesis
- neural plate
- secondary embryo
Primary Embryonic Induction
- The dorsal lip from an early T. taeniatus gastrula was removed and implanted into the __ of an early T. cristatus gastrula.
- The dorsal lip tissue __ and __ beneath the vegetal cells.
- It continued to __ into __ and other __ structures.
- Host cells became __ they normally would not have formed.
- ventral epidermis region
- invaginated and disappeared
- self-differentiate
- chordamesoderm (notochord)
- mesodermal
- organs
invaginated: be turned inside out or folded back on itself to form a cavity or pouch.
Primary Embryonic Induction
The dorsal lip of a T. taeniatus gastrula was implanted into the __ region of a T. cristatus gastrula. The dorsal lip tissue then invaginated, showing __, and later differentiated into __ and other mesodermal structures.
T. taeniatus and T. cristatus Experiment
- Ventral epidermis (belly skin)
- Self-determination
- Chordamesoderm (notochord)
Primary Embryonic Induction
- Dorsal lip cells and their derivatives (__ and __) act as the __ because:
- They induce the host’s ventral tissues to change their fates, forming a __ and __ (__).
- They organize both __ and __ tissues into a __ with clear anterior-posterior and dorsal-ventral axes.
- During normal development, these cells “organize” the __ into a __ and transform the flanking mesoderm into the anterior-posterior body axis (Spemann, 1938).
Hans Spemann and Hilde Mangold’s discovery about the dorsal lip
- notochord and head endomesoderm
- organizer
- neural tube
- dorsal mesodermal tissue (somites)
- host and donor
- secondary embryo
- dorsal ectoderm
- neural tube
a key induction process in which the progeny of dorsal lip cells induce the formation of the dorsal axis and the neural tube.
Primary embryonic induction
Molecular Bases of Induction
Who demonstrated that the dorsal lip of the blastopore, along with the dorsal mesoderm and pharyngeal endoderm that arise from it, constitutes an “organizer” capable of instructing the formation of embryonic axes? (2)
Molecular Mechanisms of Amphibian Axis Formation
- Hans Spemann
- Hilde Mangold
Molecular Bases of Induction
Spemann and Mangold demonstrated that the __, along with the __ and __ that arise from it, constitutes an “__” capable of instructing the formation of __.
Molecular Mechanisms of Amphibian Axis Formation
- dorsal lip of the blastopore
- dorsal mesoderm
- pharyngeal endoderm
- organizer
- embryonic axes
Primary Embryonic Induction
How does the organizer form?
These cells are in the right place at the right time, at a point where two signals __:
1. First signal – tells the cells that they are __.
2. Second signal – specifies that these cells are __.
These signals interact to establish a __ within the __, which serves as the foundation for specifying the __ and establishing __.
Molecular Mechanisms of Amphibian Axis Formation
- converge
- dorsal
- mesoderm
- polarity
- mesoderm
- organizer
- dorsal-ventral polarity
Primary Embryonic Induction
- They demonstrated that vegetal endoderm induces mesoderm.
- When animal cap cells were combined with vegetal cells, mesodermal differentiation occurred.
Molecular Mechanisms of Amphibian Axis Formation
- Nieuwkoop
- Nakamura
- Takasaki
Primary Embryonic Induction
Experiments by Nieuwkoop and by Nakamura and Takasaki, demonstrating mesodermal induction by vegetal endoderm:
- Isolated __ develop into a mass of ciliated __, equatorial (marginal zone) cells form __, and isolated vegetal cells generate __.
- When __ are combined with __, many of the animal cells differentiate into __.
Molecular Mechanisms of Amphibian Axis Formation
- animal cap cells
- ectoderm
- mesoderm
- gut-like tissue
- animal cap cells
- vegetal cap cells
- mesodermal tissue
Primary Embryonic Induction
Experiments by Nieuwkoop and by Nakamura and Takasaki, demonstrating mesodermal induction by vegetal endoderm:
Simplified model of mesoderm induction in Xenopus:
* A __ signal (likely a complex set of signals from activin-like __ and __) is released throughout the __ region of the embryo, inducing __ cells to become __.
* On the __ side (opposite the point of sperm entry), a __ signal is released by the __ cells of the __, inducing the formation of the __ in the overlying marginal zone cells. (C after De Robertis et al., 1992).
Molecular Mechanisms of Amphibian Axis Formation
- ventral
- TGF-β factors and FGFs
- vegetal
- marginal
- mesoderm
- dorsal
- dorsal
- vegetal
- Nieuwkoop center
- Spemann organizer
Primary Embryonic Induction
- Consists of the dorsalmost vegetal cells of the blastula.
- It is capable of inducing the organizer.
- When these cells are transplanted into the ventral vegetal side of another blastula, two embryonic axes form.
Molecular Mechanisms of Amphibian Axis Formation
Nieuwkoop Center
Primary Embryonic Induction
- They recombined single vegetal blastomeres from a 32-cell Xenopus embryo with fluorescently labeled animal pole cells.
- The dorsalmost vegetal cell induced dorsal mesoderm.
- The remaining vegetal cells induced either intermediate or ventral mesodermal tissues.
Molecular Mechanisms of Amphibian Axis Formation
Dale and Slack’s (1987)
Primary Embryonic Induction
- can act as an anchor for cadherins or as a nuclear transcription factor in the Wnt pathway.
- It specifies the micromeres in sea urchin embryos.
- It plays a key role in dorsal amphibian tissue formation.
Molecular Mechanisms of Amphibian Axis Formation: dorsal-ventral axis
micromeres are small blastomeres formed during unequal cleavage at the 16-cell stage
β-catenin
Primary Embryonic Induction
- Depletion of β-catenin leads to the loss of __ structures.
- Injection of β-catenin into the ventral side induces a __.
Molecular Mechanisms of Amphibian Axis Formation: dorsal-ventral axis
- dorsal
- secondary axis
Primary Embryonic Induction
____ refers to the initial, fundamental body axes (like anterior-posterior and dorsal-ventral) established early in embryonic development, while ____ refers to axes that arise later or are influenced by the primary axes.
- primary axis
- secondary axis
Primary Embryonic Induction
How β-catenin localize within the embryo:
* At the __ stage, β-catenin is found on the dorsal surface.
* In the __, β-catenin localizes in dorsal nuclei but not in ventral nuclei.
* This dorsal localization persists into the __ stage.
Role of Wnt Pathway Proteins in Dorsal-Ventral Axis Specification
- 2-cell
- blastula
- gastrula
- It is self-differentiating tissue.
- It induces adjacent tissues to change fates and form the neural tube and somites.
- It organizes host and donor tissues into an embryo with clear anterior-posterior and dorsal-ventral axes.
Dorsal Lip of the Blastopore (DLB)
How does transplantation of the DLB affect axis formation?
- When transplanted in early gastrula, the DLB induces dorsal structures.
- Twin embryos may form due to this induction.
Regional Specificity of Induction
- The archenteron roof induces __ and __.
- The head region induces __, __, __, and __.
- The __ and __ are also specified.
- balancers and oral apparatus
- eyes, nose, otic vesicle, and balancers.
- hindbrain
- dorsal trunk-tail mesoderm
Sets up the dorso-ventral axis polarity in the blastula.
Dorsalmost vegetal cells of the blastula can induce animal cells to become dorsal mesodermal tissue (organizer).
Nieuwkoop Center
the __ serves as an inducer because it emits signaling molecules that direct the fate of adjacent cells, thereby establishing the necessary conditions for dorsal mesodermal tissue formation and organizing the overall body plan of the embryo.
Nieuwkoop Center
Nieuwkoop Center: Left-Right Specification in Xenopus
- __ toward the sperm entry point defines the midline of the embryo.
- __ lies at the center & will give rise to the left & right sides.
- Cortical rotation
- Nieuwkoop Center
What is the model for the induction of the organizer?
β-Catenin + Tcf-3 → siamois protein + TGF-β → Goosecoid
- Goosecoid (Gsc) is a homeobox protein, a transcription factor involved in morphogenesis, particularly in the formation and patterning of embryos, and is expressed in the dorsal side of the embryo. It plays a crucial role in the Spemann-Mangold organizer phenomenon in Xenopus and is involved in organizer function, acting as a repressor of ventral fates.
- Siamois is a Xenopus homeobox gene and protein crucial for forming the Spemann’s organizer, a key region that directs embryonic development, and is a target of the Wnt signaling pathway.
Mesoderm Induction
- They establish a concentration gradient that determines mesoderm differentiation.
- Higher concentrations induce dorsal mesoderm.
- Lower concentrations promote ventral mesoderm.
Nodal-related proteins
Mesoderm Induction via Gradient in Nodal-Related Proteins
Mesoderm Induction via Gradient in Nodal-Related Proteins
- Higher concentrations induce __.
- Lower concentrations promote __.
- dorsal mesoderm
- ventral mesoderm
β-Catenin can act as an anchor for cell membrane __ or as a __ (induced by the __ pathway).
- Cadherins
- Nuclear transcription factor
- Wnt
The Nieuwkoop Center lies at the __ and will give rise to the __ and __ sides.
- Center
- Left
- Right
Cortical rotation toward the __ defines the __ of the embryo.
- Sperm entry point
- Midline
Induction by Nieuwkoop Center
The dorsalmost __ cells of the blastula can induce __ cells to become __.
- Vegetal
- Animal
- Dorsal mesodermal tissue (organizer)
Nieuwkoop Center Function
The Nieuwkoop Center sets up the __ polarity in the blastula.
Dorso-ventral axis
involves ligand-receptor interactions that trigger intracellular pathways leading to specific cellular responses.
Cell signaling
Cell Signaling
what types of mechanisms are included in cell signaling? (4)
- paracrine signaling
- autocrine signaling
- juxtacrine signaling
- endocrine signaling
- paracrine signaling targets nearby cells
- autocrine signaling targets the same cell
- juxtacrine signaling involves direct cell-to-cell contact
- endocrine signaling uses hormones in the bloodstream to reach distant cells.
Cell Signaling
Which pathways are crucial for embryonic development? (4)
- Wnt pathways
- TGF-β pathways
- BMP pathways
- FGF pathways
Cell Signaling
acts as an anchor for cell membrane cadherins or as a nuclear transcription factor induced by the Wnt pathway. It stabilizes dorsally during cortical rotation, activates dorsal mesodermal genes like Goosecoid, and specifies the organizer for head formation.
β-catenin
Cell signaling: Embryonic Development
specifies the organizer and promotes head formation. When this mRNA is injected into ventral vegetal cells at the 16-cell stage, it induces the formation of a secondary axis.
Goosecoid
Cell Signaling: Embryonic Induction
promotes the formation of structures like the cement gland, eyes, and nasal placode while inhibiting Nodal, Wnt, and BMP4 signaling pathways.
Cerberus
Cell Signaling
act as ventral mesoderm inducers and are antagonistic to the effects of Cerberus. (2)
BMP4 and Wnt
induce complete axial duplication and ectopic axis formation, leading to the development of structures such as the notochord, somites, and central nervous system (CNS). (2)
Siamois and Twin proteins
__ such as VegT and β-catenin contribute to the Nieuwkoop center organizer, while factors like Vg1, XWnt8, Activin, and Siamois are involved in establishing the organizer.
Maternal factors
Maternal factors such as VegT and β-catenin contribute to the __, while factors like Vg1, XWnt8, Activin, and Siamois are involved in establishing the __.
- Nieuwkoop center organizer
- organizer
Mesoderm Induction
__ is necessary but not sufficient for the induction of the trunk and posterior region, while __ is important for dorsalizing mesoderm.
- FGF
- Goosecoid
Mesoderm Fates
__ proteins, such as Nodal and Activin, pattern mesodermal fates by specifying different developmental pathways.
TGF-β
Cell Signaling: Embryonic Development
crucial for dorsoventral patterning of the neural tube, influencing the differentiation and organization of neural structures.
SHH (Sonic Hedgehog) signaling
process of antero-posterior axis specification in chick embryos
The antero-posterior axis is defined by the __, where primitive streak development occurs, establishing bilateral symmetry through gravity and yolk component rotation.
Posterior Marginal Zone
the reversal of internal organ positions, established by genetic and epigenetic cascades. It occurs in about 1 in 10,000 humans and is usually asymptomatic.
Situs inversus
gene control mechanisms of left-right asymmetry in organ positioning
- __ activates ActR, leading to __ expression on the right side of the node.
- Lefty inhibits signals on the midline while promoting left-sided SHH, Nodal, and Pitx2 expression, with the iv gene specifying __.
- Activin
- SHH
- organ handedness
Left-Right Assymetry
results from a dynein defect leading to immotile cilia, causing respiratory issues and contributing to abnormalities in left-right organ positioning.
Kartagener’s syndrome
- Condition where normal and inverted asymmetry coexist in the same organism.
- Caused by mutations in iv/lrd genes.
Heterotaxy
Gene Control of Left-Right Assymetry
__ of iv gene leads to random organ positioning.
Homozygous mutation
Normal Heart Looping
- Loops to the __.
- Heart treated with __ (ATPase inhibitor) disrupts left-right patterning.
- left
- lansoprazole
Left-Right Assymetry of Internal Organs
- Heart points to the __.
- Left lung has __ lobes, right lung has __.
- Gut rotation results in a __-sided stomach.
- Other examples: spleen, pancreas.
- Organ handedness is specified by the __.
- left
- two; three
- right
- iv gene
- Appears as a midline thickening of epiblast cells.
- Defines the body’s major axes and initiates gastrulation.
Human Primitive Streak
AXES DETERMINATION IN CHICK EMBRYO
- Earliest sign of left-right axis polarity in mouse embryo:
- Surge of __ on the left side of the node.
calcium ions
