Dorsalization of mesoderm induction by lithium

Area of Science:

• Developmental biology
• Embryology
• Cell biology

Background:

• Lithium administration at the 32-cell stage dorsalizes the body plan in Xenopus embryos.
• The vegetal-most tier 4 cells induce dorsal development in overlying tier 3 cells.
• Understanding lithium's mechanism requires identifying its target in mesoderm induction.

Purpose of the Study:

• To determine the effects of lithium on mesoderm induction in Xenopus embryos.
• To localize the specific cellular target of lithium's dorsalizing action.
• To elucidate how lithium modifies responses to mesoderm induction signals.

Main Methods:

• Microinjection of lithium into tier 3 or tier 4 cells of UV-irradiated embryos.
• Lineage tracer studies to track cell contributions to axial structures.
• Sandwich explant assays with animal caps and vegetal cells.
• Analysis of fibroblast growth factor-mediated mesoderm induction.

Main Results:

• Microinjection of lithium into tier 3 or tier 4 cells rescued normal development in deficient embryos.
• Cells injected into tier 3 contributed to dorsal axial structures; tier 4 injections yielded endoderm.
• Lithium pretreatment of explant components induced muscle formation.
• Lithium modified fibroblast growth factor signaling, favoring muscle over ventral mesoderm induction.

Conclusions:

• Lithium dorsalizes the response of animal cells to mesoderm induction signals.
• Lithium does not act as a direct mesoderm inducer.
• The third tier of cells in the 32-cell Xenopus embryo is the probable target of lithium action.