Enteric neurons and ganglia are derived from vagal and sacral neural crest cells, which undergo migration from the neural tube to the gut wall. In the gut wall, they first undergo rostrocaudal migration followed by migration from the superficial to deep layers. After migration, they proliferate and differentiate into the enteric plexus. Expression of the Rearranged During Transfection (RET) gene and its protein RET plays a crucial role in the formation of enteric neurons. This review describes the molecular mechanism by which the RET gene and the RET protein influence the development of enteric neurons. Vagal neural crest cells give rise to enteric neurons and glia of the foregut and midgut while sacral neural crest cells give rise to neurons of the hindgut. Interaction of RET protein with its ligands (glial cell derived neurotrophic factor (GDNF), neurturin (NRTN), and artemin (ARTN)) and its co-receptors (GDNF receptor alpha proteins (GFRα1-4)) activates the Phosphoinositide-3-kinase-protein kinase B (PI3K-PKB/AKT), RAS mitogen-activated protein kinase (RAS/MAPK) and phospholipase Cγ (PLCγ) signaling pathways, which control the survival, migration, proliferation, differentiation, and maturation of the vagal and sacral neural crest cells into enteric neurons. Abnormalities of the RET gene result in Hirschsprung's disease.
Citation: Chacchu Bhattarai, Phanindra Prasad Poudel, Arnab Ghosh, Sneha Guruprasad Kalthur. The RET gene encodes RET protein, which triggers intracellular signaling pathways for enteric neurogenesis, and RET mutation results in Hirschsprung's disease[J]. AIMS Neuroscience, 2022, 9(1): 128-149. doi: 10.3934/Neuroscience.2022008
Enteric neurons and ganglia are derived from vagal and sacral neural crest cells, which undergo migration from the neural tube to the gut wall. In the gut wall, they first undergo rostrocaudal migration followed by migration from the superficial to deep layers. After migration, they proliferate and differentiate into the enteric plexus. Expression of the Rearranged During Transfection (RET) gene and its protein RET plays a crucial role in the formation of enteric neurons. This review describes the molecular mechanism by which the RET gene and the RET protein influence the development of enteric neurons. Vagal neural crest cells give rise to enteric neurons and glia of the foregut and midgut while sacral neural crest cells give rise to neurons of the hindgut. Interaction of RET protein with its ligands (glial cell derived neurotrophic factor (GDNF), neurturin (NRTN), and artemin (ARTN)) and its co-receptors (GDNF receptor alpha proteins (GFRα1-4)) activates the Phosphoinositide-3-kinase-protein kinase B (PI3K-PKB/AKT), RAS mitogen-activated protein kinase (RAS/MAPK) and phospholipase Cγ (PLCγ) signaling pathways, which control the survival, migration, proliferation, differentiation, and maturation of the vagal and sacral neural crest cells into enteric neurons. Abnormalities of the RET gene result in Hirschsprung's disease.
Activating protein 1
Artemin
Activating transcription factor 2
Big MAP kinase
Calcium calmodulin-dependent kinase II
Cool-associated tyrosine-phosphorylated
C-Jun N-terminal kinase
Cadherin-like domain
E-twenty-six (ETS)-like transcription factor 1
E-twenty-six (ETS)-like transcription factor 7
Extracellular signal-regulated kinase
E 2 transcription factor
Glial cell-derived neurotrophic factor
Guanosine diphosphate
Guanine nucleotide exchange factor
Glial cell derived neurotrophic factor receptor alpha proteins 1-4
Glycosylphosphatidylinositol
Growth factor bound receptor protein 2
Guanosine triphosphate
Inositol 1,4,5-triphosphate receptor
Inositol 1,4,5-triphosphate
Jun N-terminal kinase
Mitogen activated protein kinase
Mitogen activated protein kinase kinases
Mitogen activated protein kinase kinase kinases
Myocyte enhancer transcription factor 2
Mitogen activated protein kinase-extracellular signal related kinase
Mitogen activated protein kinase kinase-extracellular signal related kinase kinase 1-4
Mitogen activated protein kinase kinase 3
Mitogen activated protein kinase kinase 4
Mitogen activated protein kinase kinase 6
Mitogen activated protein kinase kinase 7
Mixed lineage protein kinase 3
Mammalian target of rapamycin
Myelocytomatosis transcription factor
Neurturin
3-phosphoinositide-dependent protein kinase 1
Phosphatidylinositol (4,5)-bisphosphate
Phosphatidylinositol (3,4,5)-trisphosphate
Phosphoinositide-3-kinase
Protein kinase B
Phospholipase Cγ
Persephin
Phosphotyrosine-binding domain
p38 mitogen-activated protein kinase
Ras-related C3 botulinum toxin substrate
Rapidly accelerated fibrosarcoma
Rat Sarcoma Virus
Ras mitogen-activated protein kinase
Rearranged during transfection
Ribosomal S6 kinases
Serum- and glucocorticoid-inducible kinase
Src homolog 2
Src homolog 3
Son of sevenless
Specificity protein transcription factor 1
Transforming growth factor-β-activated kinase 1
Transforming growth factor-β
Tyrosine
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Figures(3) / Tables(11)
Chacchu Bhattarai, Phanindra Prasad Poudel, Arnab Ghosh, Sneha Guruprasad Kalthur. The RET gene encodes RET protein, which triggers intracellular signaling pathways for enteric neurogenesis, and RET mutation results in Hirschsprung's disease[J]. AIMS Neuroscience, 2022, 9(1): 128-149. doi: 10.3934/Neuroscience.2022008
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