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Fate Maps of Neural Crest and Mesoderm in the Mammalian Eye

¹From the Departments of Ophthalmology and Visual Sciences, ²Cell and Developmental Biology, and ³Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan; and the ⁴Department of Cell and Molecular Biology, Lund University, Lund, Sweden.

PURPOSE. Structures derived from periocular mesenchyme arise by complex interactions between neural crest and mesoderm. Defects in development or function of structures derived from periocular mesenchyme result in debilitating vision loss, including glaucoma. The determination of long-term fates for neural crest and mesoderm in mammals has been inhibited by the lack of suitable marking systems. In the present study, the first long-term fate maps are presented for neural crest and mesoderm in a mammalian eye.

METHODS. Complementary binary genetic approaches were used to mark indelibly the neural crest and mesoderm in the developing eye. Component one is a transgene expressing Cre recombinase under the control of an appropriate tissue-specific promoter. The second component is the conditional Cre reporter R26R, which is activated by the Cre recombinase expressed from the transgene. Lineage-marked cells were counterstained for expression of key transcription factors.

RESULTS. The results established that fates of neural crest and mesoderm in mice were similar to but not identical with those in birds. They also showed that five early transcription factor genes are expressed in unique patterns in fate-marked neural crest and mesoderm during early ocular development.

CONCLUSIONS. The data provide essential new information toward understanding the complex interactions required for normal development and function of the mammalian eye. The results also underscore the importance of confirming neural crest and mesoderm fates in a model mammalian system. The complementary systems used in this study should be useful for studying the respective cell fates in other organ systems.

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