Target type: biologicalprocess
The regionalization process that creates areas within the forebrain that will direct the behavior of cell migration in differentiation as the telencephalon develops. [GO_REF:0000021, GOC:cls, GOC:dgh, GOC:dph, GOC:jid, GOC:mgi_curators]
The telencephalon, the most rostral part of the brain, undergoes complex regionalization during development to form distinct functional areas. This process is tightly regulated by intricate interactions between signaling molecules, transcription factors, and cell-cell interactions.
**1. Early Patterning:**
* The telencephalon initially develops as a single, undifferentiated vesicle.
* **Shh** (Sonic hedgehog) signaling from the ventral midline, the **floor plate**, acts as a key morphogen, establishing a dorsal-ventral (DV) axis.
* **BMPs** (Bone morphogenetic proteins) from the dorsal midline, the **roof plate**, antagonize Shh, contributing to DV patterning.
**2. Dorsal-Ventral Patterning:**
* The DV axis is further refined by distinct transcription factor expression domains.
* **High Shh levels** induce expression of **Nkx2.1**, specifying **ventral telencephalic regions**, including the basal ganglia and septum.
* **Intermediate Shh levels** induce **Gsh2** expression, defining the **intermediate telencephalon**, containing the amygdala and hippocampus.
* **Low Shh levels** lead to **Pax6** expression, marking **dorsal telencephalic regions**, including the cerebral cortex.
**3. Cortical Regionalization:**
* The dorsal telencephalon, destined to become the cerebral cortex, undergoes further regionalization into distinct cortical areas.
* **Gradients of FGF** (Fibroblast growth factor) signaling from the anterior-posterior (AP) axis establish a **proximodistal (PD)** axis.
* **FGF signaling** promotes the development of **anterior** cortical regions, while **posterior** regions are characterized by low FGF levels.
* **Transcription factors**, including **Emx2** and **Pax6**, are expressed in specific AP domains and contribute to regional identity.
**4. Cell Fate Determination:**
* Within each cortical region, **progenitor cells** undergo **neurogenesis** and **gliogenesis**, generating diverse neuron types.
* **Transcription factors** and **signaling molecules** regulate the timing and location of cell differentiation.
**5. Synaptogenesis and Circuit Formation:**
* After neuronal generation, axons and dendrites extend, forming connections with other neurons.
* **Synaptic plasticity** and **activity-dependent refinement** shape functional circuits.
**6. Myelination:**
* **Oligodendrocytes** produce myelin, a fatty sheath that insulates axons, improving signal transmission.
* Myelination is essential for proper brain function and continues throughout development and into adulthood.
**7. Adult Neurogenesis:**
* While most neurons are generated during development, some regions, like the hippocampus, retain the capacity for **adult neurogenesis**, contributing to learning and memory.
The intricate interplay of these molecular and cellular processes ensures the precise regionalization of the telencephalon, leading to the formation of the highly complex and specialized brain regions that underlie our cognitive abilities.'
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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) |
Bone morphogenetic protein 4 | A bone morphogenetic protein 4 that is encoded in the genome of human. [PRO:CNA, UniProtKB:P12644] | 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 | ||
dorsomorphin | dorsomorphin : A pyrazolopyrimidine that is pyrazolo[1,5-a]pyrimidine which is substituted at positions 3 and 6 by pyridin-4-yl and p-[2-(piperidin-1-yl)ethoxy]phenyl groups, respectively. It is a potent, selective, reversible, and ATP-competitive inhibitor of AMPK (AMP-activated protein kinase, EC 2.7.11.31) and a selective inhibitor of bone morphogenetic protein (BMP) signaling. dorsomorphin: an AMPK inhibitor | aromatic ether; piperidines; pyrazolopyrimidine; pyridines | bone morphogenetic protein receptor antagonist; EC 2.7.11.31 {[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase} inhibitor |
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 | ||
ldn 193189 | LDN 193189: inhibits bone morphogenetic protein signaling | pyrimidines | |
ml347 | ML347: an ALK2 inhibitor; structure in first source |