lec 4 Flashcards
What major event begins in the third week of development?
Gastrulation
Gastrulation is a crucial process that transforms the bilaminar embryonic disc into a trilaminar structure.
What structure forms at the caudal end of the bilaminar embryonic disc during gastrulation?
Primitive streak
The primitive streak is essential for defining body axes and facilitating cell migration.
What is the cranial end of the primitive streak called?
Primitive node
The primitive node contains the primitive pit and is involved in cell migration.
What are the areas where cells leave the primitive streak called?
Primitive pit and groove
These represent the sites of cell ingress into the embryonic disc.
What germ layer is formed when cells replace the original hypoblast cells?
Definitive endoderm
The definitive endoderm is crucial for forming the gut lining.
What is formed by cells migrating bilaterally from the primitive streak?
Intraembryonic mesoderm
The intraembryonic mesoderm contributes to various structures, including the urogenital system.
What are the three primary germ layers formed during gastrulation?
- Ectoderm
- Mesoderm
- Endoderm
These layers are the building blocks for organ rudiments.
What major body axes are defined with the formation of the primitive streak?
- Cranial-caudal axis
- Dorsal-ventral axis
- Left-right axis
These axes help establish the overall body plan.
What is the process called when cells move through the primitive streak into the embryo?
Ingression
Ingression is a key mechanism during gastrulation.
What structure is the rudiment of the notochord formed from?
Notochordal process
The notochord plays a significant role in the development of the vertebral column.
What is the significance of neural induction during gastrulation?
It induces the ectoderm to thicken into the neural plate
The neural plate is the precursor to the central nervous system.
Fill in the blank: The oropharyngeal membrane forms just cranial to the endoderm that will form the _______.
Foregut
The oropharyngeal membrane is a key structure in the early development of the digestive system.
What happens to the definitive endoderm during subsequent development?
It folds to form three subdivisions of the primitive gut: foregut, midgut, and hindgut
These subdivisions are essential for the formation of the gastrointestinal system.
What are the two notable membranes formed by the apposition of ectoderm and endoderm?
- Oropharyngeal membrane
- Cloacal membrane
These membranes are critical in the development of the digestive and urogenital systems.
True or False: Sirenomelia is a condition that occurs in 1 in 70,000 births.
True
Sirenomelia, also known as ‘mermaid syndrome,’ is characterized by the fusion of lower limbs.
What are the four main subdivisions of intraembryonic mesoderm?
- Cardiogenic mesoderm
- Paraxial mesoderm
- Intermediate mesoderm
- Lateral plate mesoderm
Each subdivision contributes to different organ systems and structures.
What process is described as the epithelial-to-mesenchymal transition (EMT) during gastrulation?
The transformation of epiblast cells into mesenchymal cells as they migrate through the primitive streak
EMT is crucial for the formation of the three germ layers.
What is the intraembryonic mesoderm?
A third germ layer formed from cells migrating bilaterally from the primitive streak
It consists of cardiogenic mesoderm, paraxial mesoderm, intermediate mesoderm (nephrotome), and lateral plate mesoderm.
What are the four main subdivisions of intraembryonic mesoderm?
- Cardiogenic mesoderm
- Paraxial mesoderm
- Intermediate mesoderm
- Lateral plate mesoderm
Intermediate mesoderm is also known as nephrotome.
What is the notochordal process?
A thick-walled midline tube formed from a fifth population of mesodermal cells migrating cranially from the primitive node
It plays a critical role in the development of the vertebral column.
What are the oropharyngeal and cloacal membranes?
Membranes formed by the ectoderm fusing with endoderm, becoming the blind ends of the gut tube
The oropharyngeal membrane forms the opening to the oral cavity, while the cloacal membrane forms the openings of the anus and urinary/genital tracts.
What is the process of gastrulation?
The process where epiblast cells move toward and ingress through the primitive streak to form the three definitive germ layers
The layers are ectoderm, mesoderm, and definitive endoderm.
What are morphogenetic movements?
Coordinated group movements during gastrulation, including epiboly, emboly, convergence, and extension
Convergent extension involves the rearrangement of cells to narrow and lengthen a population.
Define epiboly.
The spreading of an epithelial sheet during gastrulation
It involves the movement of epiblast cells toward and into the primitive streak.
What is emboly?
The movement of cells into the interior of an embryo, also known as internalization
It can involve individual cells or sheets of cells.
What is ingression?
A type of emboly where individual cells undergo an epithelial-to-mesenchymal transition (EMT) and internalize through the primitive streak
EMT involves changes in cell adhesion and shape.
What is the role of the Nieuwkoop center?
An early organizing center that induces the organizer, which patterns mesodermal subdivisions
It is defined by location and ability to induce the organizer.
What is the organizer in embryonic development?
A structurally distinct area that patterns the embryonic axis and mesodermal subdivisions
Examples include Hensen’s node in chick and the node in mouse.
What factors establish medial-lateral subdivisions of mesoderm?
Gradients of secreted growth factors (morphogens) induce mesodermal subdivisions
Dorsalizing factors include noggin and chordin, while ventralizing factors include Bmps and Wnts.
What happens when Bmp and Wnt signaling is high?
Lateral plate mesoderm forms
Conversely, low signaling leads to the formation of notochord.
What is organogenesis?
The process of transforming organ rudiments into organ systems
It is a major topic in developmental biology following the formation of the tube-within-a-tube body plan.
What is the significance of transcription factors in mesoderm specification?
Transcription factors are required for differentiation and maintenance of cell fate in intraembryonic mesoderm
Examples include Foxa2 and Tbx6.
True or False: All organ rudiments form from a single germ layer.
False
Organ rudiments often derive from two or more germ layers.
What is the fate of epiblast cells dependent on?
Their site of origin
Fate mapping studies reveal which subdivisions of ectoderm, endoderm, and mesoderm arise from specific epiblast regions.
What structure forms from the epiblast during gastrulation?
Ectoderm
The ectoderm is one of the three primary germ layers that form during embryonic development.
What techniques are used in fate mapping and cell lineage studies?
Fate mapping uses fluorescent dyes, while cell lineage studies mark individual cells with reporter genes
These techniques help track cell development over time.
What do prospective fate maps show?
They show the locations of prospective groups of cells before the onset of gastrulation
These maps indicate how cells are organized prior to differentiation.
What is the difference between prospective potency and prospective fate of epiblast cells?
Prospective potency refers to what cells are capable of forming, while prospective fate refers to what they are destined to form
Most cells in the epiblast are pluripotent until interactions during migration specify their fate.
During gastrulation, where do cells of the primitive node migrate to form the notochord?
Cranially at the midline
This migration is essential for notochord formation.
What is the role of the prechordal plate during embryonic development?
It forms the craniomost midline head mesoderm and acts as a signaling center for the cranial end of the neural tube
The prechordal plate is crucial for proper brain development.
What happens during the formation of the notochord?
It begins as a hollow tube that extends cranially, then transforms into a flattened plate and finally into a solid rod
The notochord serves as a structural precursor for the vertebral column.
What is the significance of the neurenteric canal during notochord formation?
It represents a transient communication between the yolk sac cavity and the amniotic cavity
This canal is involved in early development stages.
What is convergent extension in the context of notochord formation?
It is the coordinated narrowing of cells in the medial-lateral plane and lengthening in the cranial-caudal plane
This process is vital for the elongation of the notochord.
True or False: The notochord contributes to the bony elements of the spinal column.
False
The notochord is replaced by mesodermal cells during early childhood.
What embryonic axes become defined during gastrulation?
Cranial-caudal and dorsal-ventral axes
The primitive streak formation is crucial for establishing these axes.
What role does the anterior visceral endoderm play in cranial patterning?
It signals prior to the formation of the primitive streak
This signaling is essential for cranial development.
Fill in the blank: The cells that ingress from the epiblast through the primitive streak form the __________.
Mesoderm
The mesoderm is one of the three primary germ layers formed during gastrulation.
What types of mesoderm are formed from the epiblast during gastrulation?
- Paraxial mesoderm
- Intermediate mesoderm
- Lateral plate mesoderm
Each of these subdivisions plays different roles in development.
What is the fate of prospective neural crest cells during development?
They become a migratory population of ectodermal cells
Neural crest cells are important for forming various structures, including parts of the nervous system.
What structure forms as a result of signaling from the anterior visceral endoderm?
The primitive streak
This structure is crucial for the formation of the three primary germ layers.
What is handed asymmetry?
Anatomic differences on the left and right sides of the body
Examples include the stomach being on the left and the liver on the right.
How is left-right asymmetry initiated in the embryo?
Through the formation of the primitive node at the cranial end of the primitive streak.
What is the role of the notochordal plate in left-right asymmetry?
It serves as the left-right organizer (LRO) and contains motile cilia that create a leftward fluid flow.
Which genes are involved in the nodal signaling cascade for left-right asymmetry?
- nodal
- lefty
- pitx2
What happens when nodal signaling is activated in the left lateral plate mesoderm?
It leads to activation of lefty and pitx2 genes.
What is situs inversus viscerum totalis?
A rare disorder where the handedness of all viscera is reversed.
What is the inheritance pattern of the iv/iv mouse mutant?
Autosomal recessive single-gene trait.
What gene is associated with the iv mutation in mice?
Left-right dynein (Lrd).
What is the function of dyneins?
They are molecular motors that move cargo along microtubules and cause bending of cilia and flagella.
What syndrome is associated with inverted laterality and ciliary dysfunction?
Kartagener syndrome.
What is the Nodal Flow Model?
A model explaining how leftward flow activates the nodal signaling cascade at a distance.
What are exosomes in the context of left-right asymmetry?
Extracellular vesicles that may transport signals from the LRO to the left side.
What is the role of matrix metalloproteinase-21 (MMP21) in symmetry breaking?
Mutations in MMP21 account for about 5% of non-syndromic heterotaxia cases.
What is a ciliopathy?
A disease resulting from defects in cilia structure and function.
What is the fate of the paraxial mesoderm in the head region?
It forms bands of cells that become unsegmented head mesoderm.
What do somites give rise to?
- Axial skeleton
- Voluntary musculature
- Dermis of the body
When do the first pairs of somites form?
Around day 20 at the head-trunk border.
What is the final count of somites in the embryonic development?
Approximately 37 pairs.
What structures do the first four pairs of somites contribute to?
- Occipital part of the skull
- Extrinsic ocular muscles
- Muscles of the tongue
What forms the axial skeleton?
The vertebral column and part of the occipital bone of the skull
What do somites contribute to?
The axial skeleton, voluntary musculature of the neck and limbs, and dermis of the body
How many pairs of somites form in the occipital region?
First four pairs
What do the first four pairs of somites contribute to?
- Occipital part of the skull
- Extrinsic ocular muscles
- Muscles of the tongue
How many pairs of cervical somites form?
Next eight pairs
What do cervical somites contribute to?
- Occipital bone
- Cervical vertebrae
- Associated muscles
- Part of the dermis of the neck
How many pairs of thoracic somites form?
Twelve pairs
What do thoracic somites form?
- Thoracic vertebrae
- Musculature and bones of the thoracic wall
- Thoracic dermis
- Part of the abdominal wall
What do lumbar somites form?
- Abdominal dermis
- Abdominal muscles
- Lumbar vertebrae
What do sacral somites form?
The sacrum and its associated dermis and musculature
What do coccygeal somites form?
The coccyx
What is the process of somitogenesis?
Formation of somites from the presomitic mesoderm through segmentation
What is the clock and wavefront model?
A model explaining somitogenesis involving an oscillator and a traveling threshold level of expression
What gene family is involved in the segmentation clock?
Notch family
What is the role of Fgf8 in somitogenesis?
It generates a gradient that helps control the positioning of somite boundaries
What is the determination wavefront?
The threshold level of Fgf8 signaling where new somite boundaries are specified
What happens when Fgf8 protein is implanted in chick embryos?
Prevents activation of the segmentation program
What is caudal dysplasia?
A condition characterized by various degrees of lower extremity malformations and anomalies of lumbar and sacral vertebrae
What is the VATER association?
A group of anomalies including vertebral defects, anal atresia, tracheal-esophageal fistula, renal defects, and radial forearm anomalies
What can cause caudal dysplasia?
Both environmental factors and mutations
What is the role of the intermediate mesoderm?
Produces the urinary system and parts of the genital system
What does the lateral plate mesoderm give rise to?
- Mesothelial covering of visceral organs
- Inner lining of the body wall
- Parts of the limbs
What are splanchnic and somatic mesoderm?
- Splanchnic mesoderm: adjacent to endoderm, forms visceral organs
- Somatic mesoderm: adjacent to ectoderm, forms body wall and limbs
What is the significance of the brachyury gene?
A T-box–containing transcription factor expressed during the primitive streak
True or False: The somite formation cycle occurs every 90 minutes in chick embryos.
True
Fill in the blank: The process of segmentation involves the formation of _______.
[serially repeated, functionally equivalent units or segments]
What is heterochrony?
Adjustments in the timing of developmental events that give rise to morphologic changes during evolution
What can induce caudal dysplasia?
Both environmental factors and mutations
For example, insulin acts as a teratogen.
What is a teratogen?
A substance that causes malformation of the embryo or fetus
Teratogenesis is covered in Chapters 5 and 6.
Which gene mutation is associated with caudal dysplasia in mice?
Brachyury gene
It is a T-box–containing transcription factor expressed during gastrulation.
What is the first event in the development of the central nervous system?
Formation of the neural plate
This occurs on day 18 in the ectoderm just cranial to the primitive node.
What is neural induction?
The process by which ectodermal cells differentiate into neuroectoderm
Induced by the primitive node.
What do neural crest cells give rise to?
A variety of structures in the embryo
They detach during the formation of the neural tube.
What is the cranial portion of the neural plate responsible for?
Gives rise to the brain
It differentiates into forebrain, midbrain, and hindbrain.
What is the role of the organizer in neural induction?
Secretes antagonists to inhibit signaling
This includes antagonizing the Bmp signaling pathway.
What are BMP antagonists?
Molecules that prevent Bmp from binding to its receptors
Examples include noggin, chordin, follistatin, and cerberus.
What is the significance of the Nieuwkoop center?
Induces the organizer in mesoderm patterning
Its exact location in birds and mammals is uncertain.
What is the head organizer also known as?
Anterior visceral endoderm (AVE)
It patterns the head region in mouse embryos.
What is combinatorial signaling?
A mechanism involving varying amounts of signaling molecules at different levels
It is crucial for forming head, trunk, and tail structures.
What is required for head development?
Inhibition of Wnt and Bmp signaling
Loss-of-function of these inhibitors results in loss of head structures.
What is the role of Fgf8 in caudal elongation?
Stimulates differentiation of neuromesodermal stem cells into neural progenitor cells
These contribute to the elongation of the caudal neuroepithelium.
What does the tail bud contribute to?
Caudal structures of the body
This includes the caudal end of the neural tube and somites.
What distinguishes primary body development from secondary body development?
Primary involves formation of germ layers; secondary involves direct formation of organ rudiments
Tail bud contributes to secondary development.
What is cyclopia?
A defect where lambs are born with a single eye in the middle of their foreheads
Caused by the plant Veratrum californicum when eaten by pregnant ewes.
What is cyclopia?
A defect caused by the plant Veratrum californicum when eaten by pregnant ewes
Cyclopia is named after the Cyclops of Greek mythology.
What plant is responsible for cyclopia in sheep?
Veratrum californicum
Commonly known as the corn lily.
What is the compound responsible for cyclopia called?
Cyclopamine
Purified after 11 years of research.
What mutation in Drosophila led to the discovery of the hedgehog gene?
The hedgehog mutant
Characterized by pointy projections of denticle.
What is the role of the hedgehog gene?
A secreted signaling molecule
Its pathway is linked to developmental processes.
What is the mammalian ortholog of the hedgehog gene?
Sonic hedgehog (Shh)
Mutations in Shh can cause holoprosencephaly and cyclopia in humans.
How does cyclopamine affect the Shh pathway?
It inhibits the function of smoothened
Smoothened is an activator of the Shh pathway.
What developmental issues can arise from the inhibition of the Shh pathway?
Holoprosencephaly and hypotelorism
Severe cases can lead to cyclopia.
Where is Shh expressed during embryonic development?
Notochord, floor plate of the neural tube, and prechordal plate
These structures help establish the midline.
What types of cancers is cyclopamine being investigated to treat?
- Medulloblastoma
- Basal cell carcinoma
- Rhabdomyosarcoma
- Breast cancer
- Prostate cancer
Cyclopamine targets overproliferation of cells mediated by the Shh pathway.
True or False: Cyclopamine is a traditional broad-spectrum cytotoxic chemotherapy drug.
False
It is being developed as a more targeted cancer treatment.
Fill in the blank: Cyclopamine is being investigated as a _______ drug.
chemotherapeutic
It aims to provide better cancer treatments.