Homeobox Genes DataBase






Vetebrate Genes in Development:








Segment polarity gene family











En-2






Definition:

The mouse and human genomes each contain two homeo box genes,
En-1 and En-2, closely related to the Drosophila segmentation gene engrailed
(en). These genes, which presumably arose by gene duplication,
have diverged from each other, and from Drosophila en, in
both sequence and regulation. Human homeo box containing genes En-1 and
En-2 located in chr.2 and chr.7 correspondingly. In mouse embryo expression
of these genes was first detected at 8 day in overlapping bands of the
anterior neural folds. By 12 day the genes were expressed in a similar
ring of cells in the central nervous system at midbrain/hindbrain junction.
En-1 was also expressed de novo in two lateral stripes extending
the length of the hindbrain and spinal cord in the developing vertebral
column and in the tail and limb buds. These data are consistent with En-1
and En-2 genes playing a role early in development in defining spatial
domains in the CNS. Later in development the En genes may have an additional
function in neurogenesis. En-1 expression in the developing perichordal
tube suggests that it may also be involved in vertebrae assembly.


[Joyner AL; et al.Genes
Dev 1: 29-38 (1987)]


The temporally and spatially restricted expression of
the mouse Engrailed (En) genes is essential for development of the midbrain
and cerebellum. A minimum En-2 1.0 kb enhancer fragment contains multiple
positive and negative regulatory elements that function in concert to establish
the early embryonic mid-hindbrain expression. These mid-hindbrain regulatory
sequences are structurally and functionally conserved in humans. The mouse
paired-box-containing genes Pax-2, Pax-5 and Pax-8 show overlapping expression
with the En genes in the developing brain. Significantly, two DNA-binding
sites for Pax-2, Pax-5 and Pax-8 proteins have been identified in the 1.0
kb En-2 regulatory sequences: mutation of the binding sites disrupts initiation
and maintenance of expression in transgenic mice. These results present
strong molecular evidence that the Pax genes are direct upstream regulators
of En-2 in the genetic cascade controlling mid-hindbrain development. These
mouse studies, taken together with others in Drosophila and zebrafish on
the role of Pax genes in controlling expression of En family members, indicate
that a Pax-En genetic pathway has been conserved during evolution (Song,
1996).


Expression patterns:

En-1,
En-2, Pax-2 and Wnt-7a in developing murine cerebellum.







Sequences:








Regulatory Regions:








Regulatory element

Localisation of element

Trans-regulatory factor

Reference





HOX Promoter(enhancer)

5'-flanking region

PAX factors(+)

Song
et al., 1996









Regulatory Connections




Downstream Genes:








Upstream Genes:










Links:






Bibliography:

Joyner AL; Martin GR En-1 and En-2, two mouse genes with
sequence homology to the Drosophila engrailed gene: expression during embryogenesis
Genes Dev 1: 29-38 (1987)






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hox Homeobox Clusters