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Fig. 9. Possible role of Cdx protein gradients in the refinement of Hox
expression boundaries. It is proposed that the rate and extent of
co-linear activation of Hox genes (temporal co-linearity) varies with the
concentration of Cdx protein (grey). Early expression of each Hox gene
(A,B) occurs in the primitive streak/tailbud (TB), assumed here
to extend forward to the level of the node. Anterior to this, within
neurectoderm, presomitic, somitic and lateral plate mesoderms, each Cdx
protein forms a posterior-to-anterior gradient by time-dependent decay. A Hox
gene with high sensitivity to Cdx dose may become progressively activated
along the Cdx gradient in a spreading wave that moves forward ahead of cell
position (such as Hox1, blue in B). An example would be Hoxb8
expression in the mouse neural tube
(Forlani et al., 2003). The
spreading wave stops when Cdx protein concentration becomes limiting, and the
time at which this occurs is influenced by the continuous regression of the
Cdx gradient. A Hox gene less sensitive to Cdx dose may not spread forward,
and may indeed show some posterior regression relative to cell position owing
to Cdx gradient regression (Hox2, red in C). Examples here might be
Hoxb8 expression in mouse paraxial mesoderm
(Forlani et al., 2003) and
Hoxb9 expression in chick neurectoderm
(Bel-Vialar et al., 2002). The
Cdx morphogen gradient may thus operate by adjusting Hox boundaries forwards
or backwards according to Hox gene sensitivities. We assume here that similar
mechanisms operate in neural and mesoderm tissues, and the more anterior Hox
boundaries in neural tissue may then be explained by the more anterior
boundaries of Cdx proteins in neural versus mesoderm tissues
(Fig. 4). At a specific point
in the maturation of neural and mesoderm tissues, it is envisaged that the
boundaries of Hox gene expression become fixed by mechanisms such as auto- and
crossregulation between Hox genes and their products
(Gould et al., 1997;
Zappavigna et al., 1991),
and/or by establishment of the Polycomb silencing mechanism
(Akasaka et al., 2001).
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