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Development 2021 Feb 16;1484:. doi: 10.1242/dev.193227.
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Retinoic acid production, regulation and containment through Zic1, Pitx2c and Cyp26c1 control cranial placode specification.

Dubey A , Yu J , Liu T , Kane MA , Saint-Jeannet JP .

All paired sensory organs arise from a common precursor domain called the pre-placodal region (PPR). In Xenopus, Zic1 non-cell autonomously regulates PPR formation by activating retinoic acid (RA) production. Here, we have identified two Zic1 targets, the RA catabolizing enzyme Cyp26c1 and the transcription factor Pitx2c, expressed in the vicinity of the PPR as being crucially required for maintaining low RA levels in a spatially restricted, PPR-adjacent domain. Morpholino- or CRISPR/Cas9-mediated Cyp26c1 knockdown abrogated PPR gene expression, yielding defective cranial placodes. Direct measurement of RA levels revealed that this is mediated by a mechanism involving excess RA accumulation. Furthermore, we show that pitx2c is activated by RA and required for Cyp26c1 expression in a domain-specific manner through induction of FGF8. We propose that Zic1 anteriorly establishes a program of RA containment and regulation through activation of Cyp26c1 and Pitx2c that cooperates to promote PPR specification in a spatially restricted domain.

PubMed ID: 33531433
PMC ID: PMC7903997
Article link: Development
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: cyp26c1 dmrta1 fgf8 foxi4 hnf1b pitx2 six1 snai2 sox2 zic1
Antibodies: FITC Ab2
Morpholinos: cyp26c1 MO2 pitx2 MO1 zic1 MO1
gRNAs referenced: cyp26c1 gRNA1 cyp26c1 gRNA2

References [+] :
Abu-Abed, The retinoic acid-metabolizing enzyme, CYP26A1, is essential for normal hindbrain patterning, vertebral identity, and development of posterior structures. 2001, Pubmed