THE DANFORTH SHORT TAIL MUTATION ACTS CELL AUTONOMOUSLY IN NOTOCHORD CELLS AND VENTRAL HINDGUT ENDODERM

Danforth's short tail (Sd) is a semidominant mutation in mouse affecti ng the axial skeleton and urogenital system, The notochord is the firs t visibly abnormal structure in mutant embryos, and disintegrates begi nning around embryonic day 9.5 along its entire length, suggesting an essential role for Sd in notochord development and maintenance. Here, we report on the fate of Sd/+ and Sd/Sd cells in chimeric embryos, Up to day 9-9.5, Sd cells contributed efficiently to the notochord of chi meric embryos. In advanced day 9.5 embryos, Sd cells were less abundan t in the posterior-most region of the notochord and in the notochordal plate, During subsequent development, Sd cells were specifically lost from the notochord and replaced by wild-type cells, In Sd/+<->+/+ chi meras, the notochord appeared histologically and functionally normal, leading to a rescue of the mutant phenotype, However, strong Sd/Sd<->/+ chimeras showed malformations of the axial skeleton and urogenital system, All Sd/Sd<->+/+ chimeras with malformations of the axial skele ton also had kidney defects, whereas chimeras without vertebral column defects had highly chimeric kidneys that appeared normal, suggesting that the urogenital malformations arise secondarily to impaired poster ior development caused by the degenerating notochord, Sd mutant cells also were specifically absent from the ventral portion of the hindgut, whereas they contributed efficiently to the dorsal region, implying t he existence of distinct cell populations in the dorsal and ventral hi ndgut, Our findings demonstrate that the Sd mutation acts cell autonom ously in cells of the notochord and ventral hind gut, Sd leads to the degeneration of notochord cells and the number or allocation of notoch ord precursors from the tail bud to the notochordal plate seems impair ed, whereas notochord formation from the node appears to be unaffected .