Page last updated: 2024-10-24

proximal/distal pattern formation

Definition

Target type: biologicalprocess

The regionalization process in which specific areas of cell differentiation are determined along a proximal/distal axis. The proximal/distal axis is defined by a line that runs from main body (proximal end) of an organism outward (distal end). [GOC:dph, GOC:go_curators, GOC:isa_complete]

Proximal/distal pattern formation is a fundamental developmental process that establishes the body axis, ensuring the correct placement of structures along this axis. It involves a complex interplay of signaling pathways, transcription factors, and cell-cell interactions, all of which contribute to the formation of distinct regions with unique cellular identities.

During early development, cells in the embryo are initially undifferentiated and capable of becoming various cell types. The establishment of a proximal-distal axis provides positional information, guiding cells to adopt specific fates based on their location along this axis.

Key molecular players involved in proximal/distal pattern formation include:

* **Signaling Pathways:** These pathways convey positional information to cells.
* **Fibroblast growth factor (FGF) signaling:** Essential for limb development. Higher levels of FGF signaling are found distally, promoting the development of digits, while lower levels proximally promote the formation of the shoulder and upper arm.
* **Wnt signaling:** Plays a role in both proximal and distal patterning. Wnt signaling is important for the establishment of the limb bud and for the patterning of the proximal limb.
* **Sonic hedgehog (Shh) signaling:** A key regulator of digit formation. Shh is expressed in the zone of polarizing activity (ZPA), a signaling center located at the posterior margin of the limb bud. Shh gradients emanating from the ZPA control the formation of digits along the anterior-posterior axis, with higher concentrations promoting the formation of more posterior digits.
* **Transcription Factors:** These proteins bind to DNA, regulating gene expression and controlling the development of different cell types.
* **Hox genes:** A family of transcription factors that are crucial for establishing the identity of different segments along the body axis, including the limbs. Hox genes are expressed in specific regions along the proximal-distal axis, and their expression patterns influence the development of different structures.
* **Tbx genes:** Transcription factors that play crucial roles in limb development. Tbx4 and Tbx5 are involved in the formation of the hindlimb and forelimb, respectively.
* **Cell-Cell Interactions:** Communication between cells is essential for coordinating development.
* **Cell-matrix interactions:** Cells adhere to the extracellular matrix (ECM), which provides structural support and signaling cues. Changes in ECM composition can influence cell fate and differentiation.
* **Cell-cell adhesion:** Cells interact with each other through cell-cell junctions, which regulate cell sorting and migration.

The process of proximal/distal pattern formation is highly dynamic, involving interactions between signaling pathways, transcription factors, and cells. This intricate interplay ensures the precise development of limbs and other structures along the body axis.

Disruptions in proximal/distal pattern formation can lead to developmental abnormalities, such as limb malformations. These abnormalities can result from mutations in genes involved in signaling pathways, transcription factors, or cell-cell interactions. Studying proximal/distal pattern formation not only provides insights into normal development but also helps us understand the underlying causes of birth defects.'
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Proteins (5)

ProteinDefinitionTaxonomy
Cytochrome P450 26B1A cytochrome P450 26B1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9NR63]Homo sapiens (human)
Catenin beta-1A catenin beta-1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P35222]Homo sapiens (human)
Zinc finger protein GLI2A zinc finger protein GLI2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P10070]Homo sapiens (human)
Zinc finger protein GLI1A zinc finger protein GLI1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P08151]Homo sapiens (human)
Retinal dehydrogenase 2A retinal dehydrogenase 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O94788]Homo sapiens (human)

Compounds (22)

CompoundDefinitionClassesRoles
staurosporine aglyconestaurosporine aglycone: metabolite from culture broth of Nocardiopsis sp.; a neurotrophin antag; inhibits BDNF TrkB receptor
uvitex swnUvitex SWN: optical brightner from Ciba; structure7-aminocoumarinsfluorochrome
win 18446WIN 18446 : A carboxamide that is 1,8-diaminooctane in which a hydrogen attached to each of the amino groups has been replaced by a dichloroacetyl group. Inhibitor of aldehyde dehydrogenase 1a2 (ALDH1a2). Inhibits the biosynthesis of retinoic acid from retinol in neonatal and adult murine testis. It down-regulates sex related genes in zebrafish.organochlorine compound;
secondary carboxamide
EC 1.2.1.3 [aldehyde dehydrogenase (NAD(+))] inhibitor
liarozoleliarozole: inhibits all-trans-retinoic acid 4-hydroxylase; effective against hormone-dependent and hormone-independent tumors; R 75251 is chlorohydrate of R 61405; a potent inhibitor of retinoic acid metabolism; USAN name - liarozole fumaratebenzimidazoles
betulinic acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid
anti-HIV agent;
anti-inflammatory agent;
antimalarial;
antineoplastic agent;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
plant metabolite
salvinsalvin: a biocyclic diterpenoid; from sage and rosemary (Lamiaceae)abietane diterpenoid;
carbotricyclic compound;
catechols;
monocarboxylic acid
angiogenesis modulating agent;
anti-inflammatory agent;
antineoplastic agent;
antioxidant;
apoptosis inducer;
food preservative;
HIV protease inhibitor;
plant metabolite
toxoflavintoxoflavin : A pyrimidotriazine that is 1,6-dimethyl-1,5,6,7-tetrahydropyrimido[5,4-e][1,2,4]triazine with oxo groups at positions 5 and 7.

toxoflavin: azapteridine antibiotic; structure
carbonyl compound;
pyrimidotriazine
antibacterial agent;
antineoplastic agent;
apoptosis inducer;
bacterial metabolite;
toxin;
virulence factor;
Wnt signalling inhibitor
bexarotenebenzoic acids;
naphthalenes;
retinoid
antineoplastic agent
daidzindaidzein 7-O-beta-D-glucoside : A glycosyloxyisoflavone that is daidzein attached to a beta-D-glucopyranosyl residue at position 7 via a glycosidic linkage. It is used in the treatment of alcohol dependency (antidipsotropic).

daidzin: a potent, selective, and reversible inhibitor of human mitochondrial aldehyde dehydrogenase
7-hydroxyisoflavones 7-O-beta-D-glucoside;
hydroxyisoflavone;
monosaccharide derivative
plant metabolite
sr 11237SR 11237: structure given in first source
ceanothic acidceanothic acid: isolated from Ceanothus americanus; structure in first source
cercosporincercosporin : An organic heterohexacyclic compound that is perylo[1,12-def][1,3]dioxepine-6,11-dione substituted by hydroxy groups at positions 5 and 12, by methoxy groups at positions 7 and 10, and by 2-hydroxypropyl groups at positions 8 and 9 (the R,R-stereoisomer). It is a phytotoxin which was first isolated from the pathogenic soybean fungus, Cercospora kikuchii and later found in multiple members of the genus Cercospora.

cercosporin: phyytotoxin from Cercospora beticola Sacc; posses photodynamic action on mice, bacteria & plants
gant 61GANT 61: a sonic hedgehog pathway inhibitor and Gli inhibitor; structure in first source

GANT61 : An aminal that is hexahydropyrimidine which is substituted on each nitrogen by a 2-(dimethylamino)benzyl group, and at the aminal carbon by a pyridin-4-yl group. A Hedgehog signaling pathway and Gli protein inhibitor.
aminal;
dialkylarylamine;
pyridines;
substituted aniline;
tertiary amino compound
antineoplastic agent;
apoptosis inducer;
glioma-associated oncogene inhibitor;
Hedgehog signaling pathway inhibitor
LSM-42773aromatic ketone
7-butyl-8-[[4-(3-chlorophenyl)-1-piperazinyl]methyl]-1,3-dimethylpurine-2,6-dionepiperazines
etodolac, (-)-isomer(R)-etodolac : The R-enantiomer of etodolac. It is inactive, in contrast to the enantiomer, (S)-etodolac, which is a preferential inhibitor of cyclo-oxygenase 2 and a non-steroidal anti-inflammatory. The racemate is commonly used for the treatment of rheumatoid arthritis and osteoarthritis, and for the alleviation of postoperative pain.etodolac
zerumbonezerumbone : A sesquiterpenoid and cyclic ketone that is (1E,4E,8E)-alpha-humulene which is substituted by an oxo group at the carbon atom attached to two double bonds. It is obtained by steam distillation from a type of edible ginger, Zingiber zerumbet Smith, grown particularly in southeast Asia.

zerumbone: RN given for (E,E,E)-isomer; structure in first source
cyclic ketone;
sesquiterpenoid
anti-inflammatory agent;
glioma-associated oncogene inhibitor;
plant metabolite
r 115866N-{4-[2-ethyl-1-(1,2,4-triazol-1-yl)butyl]phenyl}-1,3-benzothiazol-2-amine : A member of the class of benzothiazoles that is 2-amino-1,3-benzothiazole in which one of the amino hydrogens is replaced by a 4-[2-ethyl-1-(1H-1,2,4-triazol-1-yl)butyl]phenyl group.

R 115866: structure in first source

talarozole : A racemate comprising equimolar amounts of (R)- and (S)-talarozole. It is used for the treatment of keratinization disorders, psoriasis and acne.
aromatic amine;
benzothiazoles;
secondary amino compound;
triazoles
ucn 1028 ccalphostin C: structure given in first source; isolated from Cladosporium cladosporioides
nsc-287088
2alpha,3beta-dihydroxy-20(29)-lupen-28-oic acid2alpha,3beta-dihydroxy-20(29)-lupen-28-oic acid : A pentacyclic triterpenoid that is betulinic acid carrying an additional alpha-hydroxy group at position 2. It has been isolated from Breynia fruticosa.

alphitolic acid: from the aerial parts of Gouania longipetala; structure in first source
dihydroxy monocarboxylic acid;
pentacyclic triterpenoid
plant metabolite
physalin fphysalin F : A physalin with antimalarial and antitumour activities isolated from Physalis angulata.

physalin F: has immunosuppressive activity; from Physalis angulata L; structure given in first source
enone;
epoxy steroid;
lactone;
physalin
antileishmanial agent;
antimalarial;
antineoplastic agent;
apoptosis inducer;
immunosuppressive agent