The roof plate is a specialized population of non-neural cells that provides vital signals for dorsal spinal cord patterning. It is induced at the junction between neural and non-neural ectoderm — a region that also generates neural crest and dI1 sensory interneurons. So how does the roof plate acquire its unique molecular and cellular characteristics? Reporting in Development, Chizhikov and Millen show that the LIM homeodomain transcription factor Lmx1a is both necessary and sufficient to induce roof plate formation. The Lmx1a gene is inactivated in the dreher mouse mutant, which fails to develop a roof plate.

Chizhikov and Millen showed that in chick and mouse embryos, Lmx1a protein is initially expressed in progenitors that give rise to roof plate and neural crest. Later in development, it becomes restricted to cells that express roof plate-specific markers such as MafB. The authors found that if they electroporated an Lmx1a-expressing construct into one side of the chick neural tube, the MafB-expressing domain was expanded. Roof plate marker expression could also be induced by Lmx1a in explants of naive neural tissue. In both cases, the ectopic MafB-expressing tissue exerted a roof plate-like patterning influence on adjacent tissue.

In the electroporated embryos, the Lmx1a-expressing cells were concentrated in the mantle zone of the neural tube, which consists largely of differentiated neurons. Also, there was a marked decrease in cell proliferation in the electroporated regions. Together, these findings indicate that Lmx1a causes neural progenitor cells to withdraw from the cell cycle, an idea that was supported by the finding that the Lmx1a-expressing domain is expanded in dreher mutant mouse embryos.

Interestingly, although the electroporated embryos expressed Lmx1a throughout the dorsoventral axis of the neural tube, only dorsal cells acquired a roof plate identity. Therefore, additional factors are probably required to make cells competent to respond to the roof plate-inducing activity of Lmx1a. Bone morphogenetic protein (Bmp) signals from the epidermal ectoderm are likely candidates — Chizhikov and Millen found that the Bmp inhibitor Noggin also inhibits the expression of Lmx1a and roof plate markers, and ectopic Bmp signalling induces both Lmx1a and MafB expression along the dorsoventral axis of the neural tube.

Lmx1a suppresses the specification of dI1 interneurons, but neural crest progenitors seem to be refractory to its effects. Therefore, although Lmx1a can account for the segregation of roof plate and dI1 lineages, further investigations will be required to find out how different lineages are generated from a progenitor population that is competent to generate both roof plate and neural crest.