Target type: biologicalprocess
The characteristic movement of trunk neural crest cells from the neural tube to other locations in the vertebrate embryo. [GOC:bf, GOC:mat, GOC:PARL, PMID:2387238]
Trunk neural crest cells (NCCs) arise from the dorsal neural tube and undergo a remarkable migratory journey, contributing to a wide array of tissues and organs in the developing vertebrate embryo. Their migration is a tightly regulated process, orchestrated by a complex interplay of intrinsic factors within the cells and extrinsic cues from their environment.
**1. Delamination and Epithelial-to-Mesenchymal Transition (EMT):** NCCs emerge from the neural tube through a process called delamination, where they detach from the epithelial layer. This involves a transition from an epithelial phenotype to a mesenchymal one, characterized by changes in cell morphology and adhesion properties. During EMT, NCCs lose their tight junctions and cell-cell adhesion molecules, while expressing mesenchymal markers and acquiring migratory competence.
**2. Guidance Cues:** NCCs navigate their intricate migratory pathways guided by a variety of cues, both attractive and repulsive. These cues can be soluble factors, such as chemoattractants and chemo-repellents, or extracellular matrix components, such as fibronectin and laminin.
* **Slit/Robo Signaling:** Slit proteins act as repulsive cues, preventing NCCs from entering inappropriate pathways. Robo receptors on NCCs bind to Slit, initiating intracellular signaling cascades that lead to cell repulsion.
* **Netrins/DCC Signaling:** Netrins are chemoattractants that guide NCCs towards specific destinations. DCC receptors on NCCs bind to netrins, triggering signaling pathways that promote cell migration and adhesion.
* **Ephrins/Eph Signaling:** Ephrins are cell surface-bound ligands that interact with Eph receptors on NCCs. This interaction can mediate both attraction and repulsion, depending on the specific Ephrin and Eph subtypes involved.
**3. Cell-Cell Interactions:** NCCs interact with each other and with surrounding cells through cell adhesion molecules and signaling pathways.
* **Cadherins:** Cadherins are cell adhesion molecules that play a role in maintaining cell-cell contact and promoting NCC migration.
* **Integrins:** Integrins are transmembrane receptors that mediate cell adhesion to the extracellular matrix. They also play a role in signaling pathways that regulate NCC migration and differentiation.
**4. Pathways of Migration:**
* **Dorsal Pathway:** NCCs migrate dorsally, along the roof plate of the neural tube, contributing to the formation of melanocytes, sensory neurons, and glial cells in the dorsal root ganglia.
* **Ventral Pathway:** NCCs migrate ventrally, through the anterior sclerotome, contributing to the formation of sympathetic ganglia, adrenal medulla cells, and Schwann cells.
* **Cranial Pathway:** NCCs migrate to the head region, giving rise to a variety of structures, including cranial ganglia, facial cartilage, and pigment cells.
**5. Differentiation:** As NCCs reach their target locations, they differentiate into a variety of cell types, depending on their position and the signals they receive from their environment. This differentiation process is regulated by a complex interplay of transcription factors, growth factors, and other signaling molecules.
**6. Clinical Significance:** Disruptions in NCC migration can lead to a variety of congenital malformations, including neural tube defects, heart defects, and craniofacial abnormalities. Understanding the intricate mechanisms underlying NCC migration is crucial for developing effective treatments for these conditions.'
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Protein | Definition | Taxonomy |
---|---|---|
Sonic hedgehog protein | A sonic hedgehog protein that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q15465] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
jervine | jervine: teratogen from Veratrum grandiflorum; RN given refers to parent cpd(3beta,23beta)-isomer; structure | piperidines | |
cyclopamine | piperidines | glioma-associated oncogene inhibitor | |
cur 61414 | CUR 61414: inhibits the hedehog signaling pathway; structure in first source | ||
gdc 0449 | HhAntag691: inhibits the hedgehog pathway and ABC transporters; has antineoplastic activity | benzamides; monochlorobenzenes; pyridines; sulfone | antineoplastic agent; Hedgehog signaling pathway inhibitor; SMO receptor antagonist; teratogenic agent |
robotnikinin | robotnikinin: binds sonic hedgehog protein to block its signaling pathway; structure in first source |