DEFINED CONCENTRATIONS OF A POSTERIORIZING SIGNAL ARE CRITICAL FOR MAFB KREISLER SEGMENTAL EXPRESSION IN THE HINDBRAIN/

It has been shown by using the quail/chick chimera system that Hox gen e expression in the hindbrain is influenced by positional signals aris ing from the environment. In order to decipher the pathway that leads to Hox gene induction, we have investigated whether a Hox gene regulat or, the leucine zipper transcription factor is itself transcriptionall y regulated by the environmental signals. This gene is normally expres sed in rhombomeres (r) 5 and 6 and their associated neural crest, MafB /Kr expression is maintained in r5/6 when grafted into the environment of r3/4. On the contrary, the environment of rhombomeres 7/8 represse s MafB/Kr expression. Thus, as previously shown for the expression of Hox genes, MafB/Kr expression is regulated by a posterior-dominant sig nal, which in this case induces the loss of expression of this gene. W e also show that the posterior signal can be transferred to the r5/6 n euroepithelium by posterior somites (somites 7 to 10) grafted laterall y to r5/6, At the r4 level, the same somites induce MafB/Kr in r4, lea ding it to behave like r5/6, The posterior environment regulates MafB/ Kr expression in the neural crest as it does in the corresponding hind brain level, showing that some positional regulatory mechanisms are sh ared by neural tube and neural crest cells. Retinoic acid beads mimic the effect produced by the somites in repressing MafB/Kr in r5/6 and p rogressively inducing it more rostrally as its concentration increases . We therefore propose that the MafB/Kr expression domain is defined b y a molecule unevenly distributed in the paraxial mesoderm, This molec ule would allow the expression of the MafB/Kr gene in a narrow window of concentration by activating its expression at a definite threshold and repressing it at higher levels, accounting for its limited domain of expression in only two rhombomeres, It thus appears that the regula tion of MafB/Kr expression in the rhombomeres could be controlled by t he same posteriorizing factor(s) as Hox genes.