Regionalized metabolic activity establishes boundaries of retinoic acid signalling.
The competence of a cell to respond to the signalling molecule retinoic acid (RA) is thought to depend largely on its repertoire of cognate zinc finger nuclear receptors. XCYP26 is an RA hydroxylase that is expressed differentially during early Xenopus development. In Xenopus embryos, XCYP26 can rescue developmental defects induced by application of exogenous RA, suggesting that the enzymatic modifications introduced inhibit RA signalling activities in vivo. Alterations in the expression pattern of a number of different molecular markers for neural development induced upon ectopic expression of XCYP26 reflect a primary function of RA signalling in hindbrain development. Progressive inactivation of RA signalling results in a stepwise anteriorization of the molecular identity of individual rhombomeres. The expression pattern of XCYP26 during gastrulation appears to define areas within the prospective neural plate that develop in response to different concentrations of RA. Taken together, these observations appear to reflect an important regulatory function of XCYP26 for RA signalling; XCYP26-mediated modification of RA modulates its signalling activity and helps to establish boundaries of differentially responsive and non-responsive territories.
Hollemann
T
T
Georg-August-Universität Göttingen, Institut für Biochemie und Molekulare Zellbiologie, Humboldtallee 23, D-37073 Göttingen, Germany.
Chen
Y
Y
Grunz
H
H
Pieler
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000943:Antigens, Differentiation; D019521:Body Patterning; D002454:Cell Differentiation; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D051767:Early Growth Response Protein 2; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins; D008969:Molecular Sequence Data; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011994:Recombinant Proteins / Q000096:biosynthesis; D012097:Repressor Proteins; D000072516:Retinoic Acid 4-Hydroxylase; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013045:Species Specificity; D014018:Tissue Distribution; D014157:Transcription Factors / Q000096:biosynthesis; D014158:Transcription, Genetic; D014212:Tretinoin / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology
D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase