Neural Crest Development and Migration
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Questions and Answers

What type of cells do neural crest cells develop into when cultured with ECM from the dorsolateral pathway?

  • Neurons
  • Fibroblasts
  • Chromaffin cells
  • Xanthophores or melanocytes (correct)

Which combination of mechanisms contributes to the final determination of cell fate in neural crest cells?

  • Pre-specification of cell fate & selection for cell survival (correct)
  • Genetic mutation and environmental stress
  • Cell fusion and cytokine release
  • Cell signaling disruption and nutrient availability

What occurs to neural crest cells cultured without ECM?

  • They differentiate into multiple cell types
  • They die quickly
  • They remain undifferentiated (correct)
  • They form only fibroblasts

What is the potential outcome when neural precursors are influenced by glucocorticoids?

<p>Expression of hormones for stress response (A)</p> Signup and view all the answers

Which signal pathway triggers transformation into an adrenergic neuron from a bipotent cell?

<p>NGF and FGF2 (C)</p> Signup and view all the answers

What describes cranial ectodermal placodes?

<p>Local and transient thickenings of the epidermal ectoderm in the head and neck (B)</p> Signup and view all the answers

In the current model of neural crest development, what is indicated by the multipotent cell's response to environmental signals?

<p>It requires both environmental signals and intrinsic properties (A)</p> Signup and view all the answers

What is the role of the ECM in the differentiation of neural crest cells?

<p>It acts as an influential factor determining the fate of differentiating cells. (A)</p> Signup and view all the answers

What initiates the migration of neural crest cells?

<p>Signaling from surrounding neural plate and epidermal tissues (D)</p> Signup and view all the answers

Which factor is NOT involved in the initial phase of neural crest cell migration?

<p>Ephrin (D)</p> Signup and view all the answers

What role does the extracellular matrix play in the migration of neural crest cells?

<p>It promotes migration through recognition and binding. (A)</p> Signup and view all the answers

Which process allows pre-migratory neural crest cells to differentiate into various neuronal types?

<p>Multipotency and environmental signals encountered during migration (D)</p> Signup and view all the answers

What does Ephrin signaling specifically limit in the context of neural crest cell migration?

<p>Overlap with neural crest cell migration pathways (C)</p> Signup and view all the answers

Which of the following is NOT a characteristic of pre-migratory neural crest cells?

<p>They lose their multipotent capability before migration. (B)</p> Signup and view all the answers

What is the main function of RhoA in the migration process of neural crest cells?

<p>Facilitates cytoskeletal changes that enable migration (A)</p> Signup and view all the answers

Neural crest cells can differentiate into which of the following types?

<p>Both adrenergic and cholinergic neurons (B)</p> Signup and view all the answers

What does the multipotency hypothesis suggest about pre-migratory neural crest cells?

<p>Their differentiation is influenced by environmental signals. (C)</p> Signup and view all the answers

Which statement best describes the selection hypothesis regarding neural crest cells?

<p>The migration pathway enhances survival of already determined cells. (D)</p> Signup and view all the answers

What did the clonal analysis of trunk neural crest cells reveal about their differentiation?

<p>Clones can contain both pigmented and unpigmented cells. (A)</p> Signup and view all the answers

What role do ECM components play in the determination of pre-migratory neural crest cells?

<p>They influence the determination of cells prior to their migration. (D)</p> Signup and view all the answers

What was the purpose of culturing pre-migratory neural crest cells on ECM-covered microcarriers in the experiment?

<p>To mimic a natural environment for differentiation. (D)</p> Signup and view all the answers

During clonal analysis, which types of cells were observed as a result of trunk neural crest cell differentiation?

<p>Both melanocytes and sympathetic neurons within clones. (B)</p> Signup and view all the answers

What was the primary finding regarding the fate of pre-migratory neural crest cells from the experimental design involving ECM?

<p>ECM enhances the proliferation and survival of determined cells. (B)</p> Signup and view all the answers

Which of the following best describes the significance of the sterile nitrocellulose microcarriers in the experiment?

<p>They absorbed ECM components to influence cell fate. (D)</p> Signup and view all the answers

Flashcards

Neural Crest Cell Migration Initiation

The process where surrounding tissues (neural plate and epidermis) trigger changes in neural crest cells, making them ready to migrate.

Neural Crest Cell Substrate Recognition

Neural crest cells recognize and interact with the extracellular matrix (ECM) of other cells. This interaction guides their path and determines the direction of migration.

Segmental Restriction (Neural Crest)

The process where Ephrin expression in the posterior sclerotome restricts the path of migrating neural crest cells.

Neural Crest Cell Multipotency

Pre-migratory neural crest cells have the ability to differentiate into various cell types, like neurons, during migration.

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Vagal Neural Crest Differentiation

Vagal neural crest cells differentiate into parasympathetic neurons, secreting and responding to acetylcholine.

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Trunk Neural Crest Differentiation

Trunk neural crest cells differentiate into sympathetic neurons, releasing norepinephrine.

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Wnt/BMP Signaling (Neural Crest)

Wnt signals induce BMP expression, a critical step in neural crest cell specification and migration, mediated by factors like FoxD3 and Slug.

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RhoA's Role in Neural Crest Migration

RhoA induces changes in neural crest cell cytoskeleton, facilitating migration through actin polymerization.

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Neural Crest Cell Fate Determination

Neural crest cells' final differentiation is influenced by both pre-specification (initial fate decision) and environmental selection for survival.

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ECM Effect on Neural Crest Cells

Extracellular matrix (ECM) from different regions guides neural crest cell differentiation. Different ECMs lead to different cell types during migration.

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Adrenal Medulla Differentiation

Adrenal medulla precursors become either adrenergic neurons or chromaffin cells, depending on signals like FGF2 and NGF, and the presence of glucocorticoids.

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Bipotent Cell

A cell with the potential to differentiate into two different cell types.

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Cranial Placodes

Transient thickenings of the epidermal ectoderm in the head and neck.

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FGF2 and NGF

Growth factors that influence neural vs. adrenomedullary cell fate.

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Glucocorticoids

Hormones inhibiting neural differentiation and inducing adrenomedullary-specific enzymes in precursor cells.

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Multipotency Hypothesis

All neural crest cells initially have the potential to become any type of neural crest derivative. Their final fate is determined by environmental cues they receive during migration.

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Selection Hypothesis

Neural crest cells are already determined before migration begins, with each population containing a mix of cells destined for specific fates. The migration pathway enhances the growth and survival of cells with the appropriate fate.

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Clonal Analysis

A technique to study cell fate by growing a single neural crest cell in culture and analyzing its descendants. It allows observing the different cell types the original cell can produce.

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Trunk Neural Crest Clones

Clonal analysis of trunk neural crest cells revealed three types of clones: all pigmented (melanocytes), all unpigmented (sympathetic neurons), and a mix of both, indicating some cells retain the potential for multiple fates.

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ECM's Role in Determination

Extracellular matrix (ECM) components along migration pathways can influence the fate of pre-migratory neural crest cells. This suggests that the environment plays a direct role in determining cell fate.

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Microcarrier Experiment

A study where microcarriers implanted along neural crest migration routes were coated with ECM. When pre-migratory cells were cultured on these carriers, their fate was influenced by the adsorbed ECM components.

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Pre-migratory Cell Determination

Pre-migratory neural crest cells are not undetermined, but rather a mix of cells already committed to specific fates. The migration environment plays a role in selecting and promoting cells with appropriate fates.

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ECM's Influence on Fate

The specific composition of the ECM along migration routes can influence the survival and proliferation of different neural crest cell types, leading to a diverse array of specialized cells.

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Study Notes

The Neural Crest

  • The neural crest is derived from cells between the epidermal ectoderm and the neural ectoderm.
  • These cells migrate to form various tissues.
  • Four functional domains exist (overlapping anatomical regions):
    • Cranial: face cartilage, bone, cranial nerves, ganglia, pharyngeal arch connective tissue.
    • Cardiac: heart arteries, connective tissue of aortic arches, melanocytes (near somites 1-3).
    • Trunk: melanocytes, dorsal root ganglia, adrenal gland, nerves surrounding the aorta (near somite 6 to the tail).
    • Vagal (neck) and Sacral (pelvic): gut enteric ganglia (near somites 1-7 and posterior to somite 28, respectively).

Neural Crest Pathways of Migration

  • Pathway 1: ventral (through sclerotomes) → all trunk neural crest derivatives except melanocytes.
  • Pathway 2: dorsolateral (between epidermis and somites) → melanocytes.

Neural Crest Migration Route

  • Pathway 1: travels ventrally through the anterior sclerotome.
  • Pathway 1 cells migrate dorsally and ventrally around the neural tube.
    • Some cells migrate through and remain associated with the sclerotome to become dorsal root ganglia (sensory neurons).
    • Some cells migrate more ventrally between the sclerotome and dermamyotome to become sympathetic ganglia or adrenal medulla.
  • Pathway 2: cells take a dorsolateral route between the epidermis and dermis.

Neural Crest Segmental Restriction

  • Pathway 1 cells migrate only through the anterior portion of the sclerotome.

Neural Crest Migration Process

  • Four steps in migration:
    • Initiation of migration
    • Substrate recognition by migrating neural crest cells
    • Differentiation
    • Final differentiation

Neural Crest Initiation of Migration

  • Surrounding neural plate and epidermal tissues induce changes in neural crest cells needed for migration.
  • Wnt signals induce BMP expression, which induces:
    • FoxD3 (necessary for specifying neural crest cells).
    • Slug (activates factors that repress Cadherin expression; breaks tight junctions, causing neural crest cells to dissociate).
    • RhoA (induces changes in neural crest cell cytoskeleton for migration through actin polymerization).

Neural Crest Substrate Recognition

  • Cells recognize extracellular matrices of other cells (fibronectins, laminins, collagens, and proteoglycans, which promote migration).
  • Ephrin is a repulsive signal responsible for segmental restriction.
    • Ephrin is expressed only by cells in the posterior sclerotome.
    • Neural crest cells express the Ephrin receptor.
  • Ephrin expression and neural crest cell migration pathways don't overlap.

Neural Crest Differentiation

  • Pre-migratory neural crest cells are multipotent (capable of differentiating into multiple cell types).
  • Vagal neural crest → parasympathetic (cholinergic) neurons.
  • Trunk neural crest → sympathetic (adrenergic) neurons.

Neural Crest Multipotency

  • One neural crest cell population can generate different neuronal types.
  • Pre-migratory cells express enzymes for synthesizing both neurotransmitters (acetylcholine & norepinephrine).
  • Differentiation depends on signals encountered during migration.

Neural Crest Models for Differentiation

  • Multipotency Hypothesis: All neural crest cells have potential to form any neural crest derivative; determination depends on environmental signals and migration pathway.
  • Selection Hypothesis: Neural crest cells are determined before migration; population is a mixture of already determined cells; environment enhances proliferation and survival of appropriately determined cells.
  • Pluripotency Hypothesis: Undetermined neural crest cells have the potential to differentiate into various cell types.

Neural Crest Clonal Analysis

  • Single neural crest cell is cultured in a medium that supports its survival and proliferation without restricting cell potency.
  • Descendants are analyzed to determine differentiated cell types based on morphology and immunostaining for characteristic proteins.
  • Cohen and Konigsberg (1975) study shows three types of clones: all pigmented, all unpigmented, and some pigmented and some unpigmented cells within the same clone. Three types of clones observed (melanocytes (pigmented), sympathetic neurons of the adrenal medulla (unpigmented), mixed).

Neural Crest Determination of Pre-migratory Cells using ECM Components

  • Sterile nitrocellulose microcarriers are implanted along main migration routes in axolotl embryos.
  • Carriers are left in embryos to adsorb ECM components for 10-12 hours.
  • Pre-migratory neural crest cells are removed and cultured on ECM-covered microcarriers for 5 days.
  • Different ECM types affect differentiation.

Neural Crest Current View

  • Before migration: Mixed population of multipotent and more restricted potential cells.
  • Final determination: Involves both pre-specification of cell fate and selection for cell survival.

Neural Crest Final Differentiation (example: Adrenal Medulla)

  • Adrenal medulla: Portion of adrenal gland that secretes catecholamines (epinephrine & norepinephrine).
    • Regulates smooth muscle, cardiac activity, glycolysis, lipolysis, and glycogenesis.
    • Part of the sympathetic "fight-or-flight" reaction.
    • Contains both adrenergic neurons and chromaffin cells (catecholamine-secreting cells).

Neural Crest Models for Differentiation of Bipotent Cell

  • Signal 1 (e.g., FGF2, NGF) can lead to a specific cell type (e.g., an adrenergic neuron).
  • Signal 2 (e.g., Glucocorticoids) can lead to a different cell type (e.g., a chromaffin cell).

Cranial Ectodermal Placodes

  • Local, transient thickenings of the epidermal ectoderm in the head and neck.
  • Derived from tissue competent to form neural structures.
  • Cells are competent for neuronal induction by neighboring tissues.
  • Sensory placodes form distal neurons of ganglia associated with hearing, balance, taste, and smell.
  • Neural crest cells contribute glial cells to these sensory ganglia.

Otic Placode Induction

  • Cranial paraxial mesoderm underlies competent ectodermal tissue, secretes Fgf19.
  • Fgf19 is received by presumptive otic vesicles and adjacent neural plate.
  • Adjacent neural plate secretes Wnt8c and Fgf3 (synergistically induce otic placode formation with Fgf19).
  • Fgf8 from endodermal regions controls Fgf19 secretion location.
  • Otic placode develops into inner ear sensory cells.

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Explore the fascinating world of the neural crest, a critical structure in vertebrate embryology. This quiz covers the origins, functional domains, and migration pathways of neural crest cells, essential for understanding their role in forming various tissues. Test your knowledge on this pivotal aspect of developmental biology.

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