Fig. 8. Model for regulation of Hoxa3 and Hoxb3 and common role for auto/cross-regulatory mechanisms in maintaining of Hox gene expression in the developing hindbrain. (A) Hox genes are grouped in paralogous relationships and listed under the column ‘Domain/gene’. The specific rhombomeric domain(s) of expression for each set of Hox genes is listed on the left. Under the column ‘Initiation’, is shown the types of factors or sites that are involved in triggering the initiation of segmental expression of the respective Hox genes in the nervous system. The ovals indicate binding sites for retinoic acid receptor elements (RARE, black); kreisler (Kr, orange); Ets factors (yellow); and Krox20 (Krox, brown). Under ‘Maintenance’ is illustrated the distribution of bipartite Hox/Pbx (HOX/PBC, blue ovals) and Meis/Prep/Hth (Meis/Hth, green box) -binding motifs that form the Hox auto or cross-regulatory elements. The purple oval for Hoxb4 indicates a homeodomain (HD) binding site necessary for auto-regulatory activity in which the factor binding has not been identified. Note that, to date, only one paralog from each group has a Hox auto/cross-regulatory response element, while they often share common types of initiation elements. For references on the identification and roles of the sites see Materials and Methods. (B) Model comparing the regulatory interactions leading to similar, yet distinct patterns in the initiation and maintenance of the segmental expression of the paralogous Hoxa3 and Hoxb3 genes. Early expression of kreisler (red) at 8.0-8.25 dpc triggers segmental expression of Hoxa3 (blue) and Hoxb3 (purple) from 8.25-9.0 dpc, via the presence of kreisler-binding sites (KrA, Kr1 and Kr1) in the genes. Unlike the r5/r6 domain of Hoxa3, Hoxb3 expression is restricted to r5, by cooperation of kreisler with Krox20 and Ets proteins. In later stages (9.0-11.5 dpc), when kreisler is downregulated, segmental expression of Hoxa3 is maintained in r5 and r6 by Hox and Pbx factors through two HOX/PBC sites that are not present in Hoxb3 control regions. Hoxb3 is expressed more posteriorly in r7 of the hindbrain via the action of a shared enhancer, with Hoxb4 itself also dependent upon Hox /Pbx interactions.