Regulation of Hoxb4 induction after neurulation by somite signal and neural competence

<p>Abstract</p> <p>Background</p> <p>While the body axis is largely patterned along the anterior-posterior (A-P) axis during gastrulation, the central nervous system (CNS) shows dynamic changes in the expression pattern of <it>Hox </it>genes during neurulation, suggesting that the CNS refines the A-P pattern continuously after neural tube formation. This study aims at clarifying the role of somites in up-regulating <it>Hoxb4 </it>expression to eventually establish its final pattern and how the neural tube develops a competence to respond to extrinsic signals.</p> <p>Results</p> <p>We show that somites are required for the up-regulation of <it>Hoxb4 </it>in the neural tube at the level of somites 1 to 5, the anterior-most domain of expression. However, each somite immediately adjacent to the neural tube is not sufficient at each level; planar signaling is additionally required particularly at the anterior-most segments of the expression domain. We also show that the dorsal side of the neural tube has a greater susceptibility to expressing <it>Hoxb4 </it>than the ventral region, a feature associated with dorsalization of the neural tube by BMP signals. BMP4 is additionally able to up-regulate <it>Hoxb4 </it>ventrally, but the effect is restricted to the axial levels at which <it>Hoxb4 </it>is normally expressed, and only in the presence of retinoic acid (RA) or somites, suggesting a role for BMP in rendering the neural tube competent to express <it>Hoxb4 </it>in response to RA or somite signals.</p> <p>Conclusion</p> <p>In identifying the collaboration between somites and neural tube competence in the induction of <it>Hoxb4</it>, this study demonstrates interplay between A-P and dorsal-ventral (D-V) patterning systems, whereby a specific feature of D-V polarity may be a prerequisite for proper A-P patterning by <it>Hox </it>genes.</p