Retinoids and Hox genes

  title={Retinoids and Hox genes},
  author={Heather Marshall and Alastair Morrison and Mich{\`e}le Studer and Heike Pöpperl and Robb Krumlauf},
  journal={The FASEB Journal},
  pages={969 - 978}
The vertebrate embryonic body plan is constructed through the interaction of many de‐ velopmentally regulated genes that supply cells with the essential positional and functional information they require to migrate to their appropriate destination and generate the proper structures. Some molecular cues involved in patterning the central nervous system, particularly in the hindbrain, are interpreted by the Hox homeobox genes. Retinoids can affect the expression of Hox genes in cell lines and… 

Retinoic acid regulates a subset of Cdx1 function in vivo

Cdx1 may serve as an intermediary in governing a subset of expression of Cdx1 crucial for normal vertebral patterning in mesodermal Hox expression, consistent with a pivotal role for retinoid signalling.

Retinoid signalling is required for information transfer from mesoderm to neuroectoderm during gastrulation.

This work shows that the retinoid receptor antagonist AGN193109 causes a posterior hindbrain defect in Xenopus, comparable to that seen in other vertebrates, and proposes that the gastrula non-organiser mesoderm and its later derivative, the paraxial Mesoderm, is the source of a retinoids, which acts as a transforming (caudalising) signal for the future posterior hind brain.

Altered retinoic acid sensitivity and temporal expression of Hox genes in polycomb-M33-deficient mice.

It is proposed that a function of the M33 protein is to control the accessibility of retinoic acid response elements in the vicinity of Hox genes regulatory regions by direct or indirect mechanisms or both, which could provide a means for preventing ectopic transactivation early in development and be part of the molecular basis for temporal colinearity of H Cox gene expression.

Retinoic Acid Regulation of Cdx1: an Indirect Mechanism for Retinoids and Vertebral Specification

Evidence that cdx1 is a direct RA target gene is presented, suggesting an additional pathway for retinoid-dependent vertebral specification and a role for Cdx members in direct regulation of expression of at least some Hox genes.

Direct crossregulation between retinoic acid receptor β and Hox genes during hindbrain segmentation

This study identifies a new molecular link, completing a feedback circuit between Rarb, Hoxb4 and Hoxd4, and proposes that the function of this circuit is to align the initially incongruent expression of multiple RA-induced genes at a single segment boundary.

Induction of Hox genes and genome wide identification of Hox binding sites in mice

The goal of this research was to investigate on a genome-wide basis, the rules and principles which underlie the binding of different HOX proteins to target sites and understand the basis for their distinct specificities.



Retinoic acid alters hindbrain Hox code and induces transformation of rhombomeres 2/3 into a 4/5 identity

Together the molecular and anatomical alterations indicate that retinoic acid has induced changes in the hindbrain Hox code which result in the homeotic transformation of rhom-bomeres (r) 2/3 to an r4/5 identity.

In vitro and transgenic analysis of a human HOXD4 retinoid-responsive enhancer.

The identification of a 185-bp retinoid-responsive transcriptional enhancer 5' of the human HOXD4 gene, which regulates inducibility of the gene in embryonal carcinoma cells through a pattern of DNA-protein interaction on at least two distinct elements, provides further support for a role of endogenous retinoids in regulation and spatial restriction of Hox gene expression in the central nervous system.

A conserved retinoic acid response element required for early expression of the homeobox gene Hoxb-1

Two enhancers, 3′ of the mouse Hoxb-1 gene, are identified, which together reconstruct the early endogenous expression pattern and mediate the early ectopic response to retinoic acid.

Ectopic expression of Hoxa-1 in the zebrafish alters the fate of the mandibular arch neural crest and phenocopies a retinoic acid-induced phenotype.

The phenotype induced by exogenous retinoic acid in the zebrafish can also be generated by the overexpression of Hoxa-1 following injection of synthetic RNA into the fertilised egg.

Retinoic acid causes abnormal development and segmental patterning of the anterior hindbrain in Xenopus embryos.

It is concluded that low doses of RA applied during gastrulation have specific effects on the anterior Xenopus hindbrain which appear to be evolutionarily conserved in the light of similar recent findings in zebrafish.

Identification of a retinoic acid response element upstream of the murine Hox-4.2 gene

Using transient expression assays, it was shown that luciferase reporter gene constructs carrying genomic sequences located upstream of Hox-4.2 responded to RA in murine P19 EC cells, and the response to RA could be inhibited by expressing a dominant negative form of RAR alpha in transfected P19EC cells.

Polarizing activity and retinoid synthesis in the floor plate of the neural tube

The results show that the floor plate is a local source of a ZPA-like polarizing signal, possibly a retinoid, which may regulate the pattern of cell differentiation in the developing CNS.

Multiple spatially specific enhancers are required to reconstruct the pattern of Hox-2.6 gene expression.

It is shown that the overall expression pattern of the endogenous Hox-2.6 gene can be reconstructed when it is isolated from the complex, and direct comparison by in situ hybridization revealed that the levels of transgene expression are similar to those ofThe endogenous gene.

Neuroectodermal autonomy of Hox-2.9 expression revealed by rhombomere transpositions

Hox-2.9 was expressed in the ectopic r4 as strongly as in the normal r4, whereas reciprocal grafts of future r2 to r4 position did not express Hox- 2.9, suggesting that Hox genes confer positional value.