Target type: biologicalprocess
The process in which the anatomical structure of the midbrain-hindbrain boundary is generated and organized. The midbrain-hindbrain domain of the embryonic brain is comprised of the mesencephalic vesicle and the first rhombencephalic vesicle at early somitogenesis stages. An organizing center at the boundary patterns the midbrain and hindbrain primordia of the neural plate. [GO_REF:0000021, GOC:cls, GOC:dgh, GOC:dph, GOC:jid, PMID:15541513]
Midbrain-hindbrain boundary morphogenesis is a crucial developmental process that establishes the distinct boundaries between these two vital regions of the central nervous system. This intricate process is orchestrated by a complex interplay of signaling pathways, transcription factors, and cell-cell interactions.
The initiation of this boundary formation is marked by the establishment of the isthmic organizer, a specialized signaling center located at the future midbrain-hindbrain boundary. This organizer is characterized by the expression of a critical transcription factor called Otx2 in the midbrain and Gbx2 in the hindbrain. The expression domains of these factors define the boundaries of the two regions.
The isthmic organizer secretes several signaling molecules, including fibroblast growth factors (FGFs), Wnt proteins, and retinoic acid (RA). These signals play crucial roles in regulating cell fate, proliferation, and migration, ensuring the proper formation of the midbrain and hindbrain.
FGFs, particularly FGF8, act as a potent organizer signal, promoting the expression of midbrain-specific genes and repressing hindbrain genes. Wnt proteins, such as Wnt1, are also expressed in the isthmic organizer and contribute to the development of the cerebellum, a critical structure of the hindbrain. RA, a morphogen, establishes a concentration gradient that influences the differentiation of neural progenitors along the anterior-posterior axis.
Cell migration and differentiation are essential processes that shape the midbrain-hindbrain boundary. Neural crest cells, multipotent cells that migrate from the neural tube, contribute to the formation of various structures, including cranial nerves and melanocytes. These cells are guided by chemoattractants and repellents, ensuring their precise localization and differentiation into specific cell types.
Furthermore, the precise positioning of the midbrain-hindbrain boundary is influenced by mechanical forces generated by the expanding neural tube. These forces contribute to the shaping and refinement of the boundary region.
The proper formation of the midbrain-hindbrain boundary is crucial for the development of a functional central nervous system. Disruptions in this process can lead to severe neurological disorders, such as cerebellar malformations and midbrain hypoplasia, highlighting the importance of this intricate developmental event.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Lysine-specific demethylase 2B | A lysine-specific demethylase 2B that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8NHM5] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| deferiprone | deferiprone : A member of the class of 4-pyridones that is pyridin-4(1H)-one substituted at positions 1 and 2 by methyl groups and at position 3 by a hydroxy group. A lipid-soluble iron-chelator used for treatment of thalassaemia. Deferiprone: A pyridone derivative and iron chelator that is used in the treatment of IRON OVERLOAD in patients with THALASSEMIA. | 4-pyridones | iron chelator; protective agent |
| 3-[[2-(2-pyridinyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-4-pyrimidinyl]amino]propanoic acid | organonitrogen heterocyclic compound |