1. Neural Crest Overview
Neural crest cells (NCCs) are a transient, multipotent population derived from the neural plate border during neurulation.
They undergo epithelial-to-mesenchymal transition (EMT) and migrate extensively to contribute to diverse cell types and tissues.
2. Types of Neural Crest Cells
The neural crest is subdivided along the anterior-posterior axis:
Cranial neural crest: Forms craniofacial cartilage, bone, and connective tissue.
Cardiac neural crest: Contributes to the outflow tract of the heart and arterial patterning.
Trunk neural crest: Produces melanocytes, sensory and sympathetic neurons, and Schwann cells.
Vagal and sacral neural crest: Forms the enteric nervous system.
3. Specification and Induction of Neural Crest Cells
Neural crest specification is a multistage process:
Neural plate border induction: Mediated by BMP, Wnt, and FGF signals.
Neural crest specification: Key transcription factors include Sox9, Sox10, and Snail2.
Gradients of signaling molecules define neural crest identity along the anterior-posterior axis.
4. Migration of Neural Crest Cells
NCCs migrate through specific pathways, guided by:
Contact-mediated interactions: Ephrins, semaphorins, and integrins.
Chemoattraction and chemorepulsion: Molecules like VEGF and Slit/Robo.
Trunk NCCs follow two major pathways:
Ventral pathway: Through the somites to form sympathetic neurons, glia, and adrenal cells.
Dorsolateral pathway: Between ectoderm and somite to form melanocytes.
5. Neural Crest Cell Differentiation
NCC fate is influenced by the environment and local signaling.
Key factors include Wnt, BMP, and Notch signaling pathways.
Neural crest plasticity decreases as cells commit to specific lineages.
7. Clinical Implications
Neurocristopathies: Diseases resulting from neural crest defects, including:
Hirschsprung’s disease: Failure of neural crest migration to the gut.
DiGeorge syndrome: Defects in cranial and cardiac neural crest derivatives.
Insights into neural crest development have implications for regenerative medicine, cancer (neuroblastomas), and congenital disorders.
The multipotency and plasticity of neural crest cells allow them to contribute to diverse tissues.
Molecular cues are critical for neural crest migration, differentiation, and axonal guidance.
Neural crest research provides foundational knowledge for understanding developmental diseases and evolutionary adaptations.
1:
How can you investigate to which tissue(s) and cell types the neural crest cells from a particular level along the anterior-posterior axis will contribute at a later stage of development? What was found in these experiments?
You can use lineage-tracing techniques to label neural crest cells at specific anterior-posterior levels and track their progeny. Common methods include:
1. DiI or fluorescent dye labeling – Injecting dyes into neural crest cells to follow their migration and final destinations.
2. Genetic labeling – Using Cre-lox or GFP reporters in transgenic animals to permanently mark neural crest cells and their descendants.
3. Chick-quail chimeras – Grafting neural tube segments from quails into chick embryos and tracing the donor cells by quail-specific markers (nukleoli sehr gut farben).
Findings:
Experiments revealed that neural crest cells are highly plastic during early stages but later become regionally restricted:
• Cranial neural crest contributes to craniofacial cartilage, bones, and nerves.
• Trunk neural crest gives rise to melanocytes, peripheral neurons, and glia. (Nur peripheres nervensystem)
• Cardiac neural crest contributes to the outflow tract of the heart. (Aufteilung aorta und lungenarterie)
Endokrine zellen (nebennierenrinde) (Schilddrüse)
Which promotor for A P axis: HOX
________________________________________
2:
What differences between cranial and trunk neural crest cells do you know?
• Cranial neural crest cells:
o Can form mesenchymal derivatives like bone and cartilage (e.g., craniofacial skeleton).
o Contribute to cranial ganglia and connective tissues.
o Have higher plasticity and multipotency.
—> keine HOX gen expression
• Trunk neural crest cells:
o Do not form skeletal tissues.
o Contribute to melanocytes, peripheral neurons, Schwann cells, and adrenal medulla cells.
o Follow distinct migration pathways such as ventral (through the somite) and dorsolateral (between the ectoderm and dermomyotome).
—> HOX gen expression (wenn inhibiert auch hier Bindegewebe Bildung möglich)
3:
What do cranial neural crest cells form?
Cranial neural crest cells form:
• Craniofacial cartilage and bones.
• Cranial ganglia (e.g., trigeminal ganglia).
• Smooth muscle of cranial blood vessels.
• Connective tissues in the head.
• Teeth (dentin-producing odontoblasts).
4:
What do the cardiac neural crest cells form?
Cardiac neural crest cells contribute to:
• The outflow tract of the heart (forming the septum between the aorta and pulmonary artery).
• Smooth muscle of major arteries (e.g., aortic arch arteries).
• Neurons and glia of the cardiac ganglia.
5:
How are neural crest cells specified? What stages can you distinguish, and what molecules are involved?
Neural crest specification involves:
1. Induction: Signals from adjacent tissues (e.g., notochord, epidermis) induce neural plate border regions. Key molecules: BMP, Wnt, FGF.
2. Neural plate border formation: Border-specific markers like Pax3 and Msx1 are expressed.
3. Neural crest specification: Upregulation of neural crest markers (e.g., Snail2, Sox9, Sox10).
Molecules involved include:
• Wnt signaling: Maintains neural crest fate.
• BMP signaling: Balances neural crest and non-neural ectoderm specification.
• FGF signaling: Enhances neural plate border induction.
6:
What changes have to occur in neural crest cells for their emigration from the neural epithelium?
Neural crest cells undergo:
1. Epithelial-to-mesenchymal transition (EMT): Loss of apical-basal polarity and cell adhesion (downregulation of E-cadherin (snail), upregulation of N-cadherin and vimentin).
2. Cytoskeletal remodeling: Actin and microtubules rearrange to allow motility. (Rho GTPasen)
3. Matrix degradation: Secretion of metalloproteinases (MMPs) to break down extracellular matrix.
Mechanische Eigenschaften des unterliegenden mesoderms verhärtet sich
7:
What triggers the delamination of neural crest cells from the neural epithelium?
• BMP signaling: Promotes EMT and cell migration.
• Wnt signaling: Maintains migratory state.
• Snail and Twist transcription factors: Downregulate adhesion molecules like E-cadherin.
8:
Explain the basic principle of adherent cell migration.
Adherent cell migration involves:
1. Cell polarization: Establishing a leading edge (protrusion) and a trailing edge.
2. Protrusion formation: Actin polymerization drives lamellipodia or filopodia forward.
3. Adhesion: Integrins form focal adhesions with the extracellular matrix.
4. Contraction: Myosin II-driven contraction pulls the cell body forward.
5. Detachment: Trailing edge adhesions release to allow forward movement.
Wanderung auf extrazellulare Matrix, andere zellen, basal Latina
9:
Which mechanisms control the initial direction of neural crest migration? What is the driving force?
• Guidance cues: Semaphorins, ephrins, and chemoattractants like VEGF guide cells.
• Substrate interactions: Integrins bind ECM molecules like fibronectin and laminin.
• Driving force: Actomyosin contractility and cytoskeletal dynamics generate the mechanical force for movement.
1st mechanism: Contact inhibition of locomotion —> können nur ventral wandern dansonst an nachbarzellen anstoßen und durch den Kontakt (cadherine) Richtung ändern
!!!
10:
What is collective cell migration?
Collective cell migration is the coordinated movement of a group of cells while maintaining cell-cell junctions oder andere Interaktionen miteinander .
—> Wundheilung, lateral line organ, placoden und neuralleisten zellen die hinterherrellen, nierenentwicklung
11:
Which types of collective cell migration do you know? Give examples.
1. Sheet migration: Epithelial sheets move as a unit (e.g., wound healing).
2. Stream migration: Neural crest cells migrate in loosely connected streams.
3. Cluster migration: Groups of cells move together (e.g., border cells in Drosophila).
12:
Explain the role of leader and follower cells in collective cell migration.
• Leader cells: Sense and respond to environmental cues, guiding the group. —> Wahrnehmung
• Follower cells: Maintain cohesion and amplify the migration of the group. —> passiv werden hinterhergezogen
13:
What controls the direction of migration in collective cell migration?
Guidance cues like chemokines, growth factors, and ECM interactions direct migration.
Gradienten, gradienten über Gegenspieler auf der rückseite)
14:
What does the chase and run model describe?
The chase-and-run model explains how chemotactic cells (e.g., placodal cells) "chase" neural crest cells producing chemoattractants, which then "run" away to maintain distance and directionality.
15:
What are the main migration pathways for trunk neural crest cells and how is this migration regulated?
• Ventral pathway: Cells migrate through the somite, forming neurons and glia.
• Dorsolateral pathway: Cells migrate between ectoderm and somite, forming melanocytes.
Regulation:
• Semaphorins and ephrins restrict specific pathways.
• ECM molecules like fibronectin promote migration.
16:
What kind of molecules are semaphorin, neuropilin, ephrin, and Eph?
• Semaphorins: Guidance molecules that mediate repulsion. Transmembran,
• Neuropilins: Receptors for semaphorins. Co Rezeptor
• Ephrins and Eph: Ligand-receptor pairs that regulate contact-dependent repulsion. (GPI Anker und tyrosinkinase Rezeptor ) (bsp: somitogenese trennen von Zell Populationen —> kompartimente bilden!!! oder axon guidance)
17:
Are premigratory neural crest cells multipotent stem cells? How can you investigate this question?
Yes, they are multipotent stem cells. This can be investigated using:
1. Clonal analysis: Single-cell culture to see if one cell produces multiple derivatives. (Schwer nur eine Zelle zu erwischen)
2. Lineage tracing: Labeling single cells and tracking their differentiation. (DyeI und dyeO)(um Einzelzellen zu markieren Fluoreszenz dextrane) (dextran injection)
brainbow System wo verteilt viele Farben vorhanden sind
18:
How is neural crest cell differentiation regulated?
Neural crest differentiation is regulated by:
• Intrinsic factors: Transcription factors like Sox10, FoxD3.
• Extrinsic signals: Wnt, BMP, and Notch pathways guide specific fates.
• Microenvironment: Local ECM and niche cues influence differentiation.
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