Neural Crest Cells(1)

Unique to vertebrates.
Arise during neurulation, positioned between epidermis and neural tube (migration stage).
Often referred to as the "4th germ layer".

Extensive Migration:
- Generate diverse cell types, including:
  - Neurons and glial cells for sensory, parasympathetic, and sympathetic nervous systems.
  - Epinephrine-producing cells of the adrenal gland (medulla).
  - Components of skeletal and connective tissue in the head.
- Fate:
  - Depends on migration paths and settling regions, influenced by environmental signals that guide cells.

Origin:
- Arise from the dorsal region of the neural tube.
Timing of Specification:
- Occurs during the formation of borders between neural and non-neural ectoderm.
Critical Signals:
- BMP and Wnt are crucial for defining boundaries.
- Expression timing is essential for the differentiation of neural plate, epidermis, and neural crest cells.
**Transcription Factors:
- Border cells express transcription factors preventing differentiation into neural plate or epidermis:
  - Pax3/7, Dlx5/6.

Transcription factors influenced by the neural plate:
- Induce a second set of specifiers in NCC, essential for further differentiation:
  - FoxD3, Sox9, Snail (premigratory).
  - Sox10 (migratory type).
Neural Crest Effectors:
- Activated by NC specifiers:
  - MITF, Col2α1, KIT (localization properties).

Initiation of migration involves detachment from tight junctions in the neural folds influenced by Snail expression.
Before migration, NCC express certain cadherins that regulate cell adhesion.
Activation of RhoA influences the cytoskeletal structure essential for migration.

Dorsolateral Pathway:
- NCC travel between epidermis and dermis, differentiating into melanocytes.
Ventral Pathway:
- Form sympathetic and sensory neurons, travel ventrally through anterior sclerotome,
- Contributes to adrenal medulla, sympathetic ganglia formation.

NCC choose migration pathways influenced by:
- Chemotactic factors and extracellular matrix components that guide movement.
- Proteins like semaphorins can inhibit or guide migration based on region.
- Decision-making is contingent on the NCC’s environment and initial specification.

Multipotency allows NCC to differentiate into cell types based on initial location and environmental cues:
- Autonomous factors (e.g., Hox genes) & environmental conditions impact the differentiation into various neuronal types or other cell types.
Cranial NCC versus Trunk NCC:
- Different functions and derivatives such as formation of jawbones or neurons in the gut.

Presence of Factors:
- Glucocorticoids can direct differentiation into specific cell types (e.g., adrenal neurons).
Lack of GDNF (glial-derived neurotrophic factor) can impede proper NCC function, leading to conditions like Hirschsprung disease.

Contributes to heart development by migrating into regions surrounding aortic arch arteries.
FGF8 acts as a chemotactic factor, influencing development.
Defects in cardiac NCC can result in congenital anomalies such as persistent truncus arteriosus.

Mutations can lead to significant phenotype variations:
- Melanoblast migration impacts pigmentation variability in species.
Notably linked to conditions like piebaldism due to critical receptor interactions preventing proper migration and proliferation of NCC.

Studies showing transplanted NC cells can give rise to different neuronal types depending on their migrated location.
Evidence of transcription factors defining NCC capabilities, further supported by lineage tracing experiments.