The anteroposterior axis is established in vertebrate embryos during gastrulation and neurulation, and it is most evident in neuroectoderm with formation of fore-, mid-, hindbrain and spinal cord. Although considerable progress has been made in understanding neuronal development or dorsoventral patterning in the neural tube, signaling mechanisms leading to the initial anteroposterior pattern in vertebrates are poorly understood. This application concerns early cell-cell interactions leading to patterning of the developing central nervous system. Many of these interactions are mediated by signaling factors produced by a special embryonic cell population known as the Spemann organizer. One of the earliest events that marks neural tissue specification and patterning is activation of the Zic3 gene in prospective neuroectoderm and later in the anterior neural plate. Flanking DNA sequences of the Xenopus Zic3 gene have been isolated to develop a reporter gene microinjection assay for analysis of the signaling pathways that control neural induction. The dependence of Zic3 activation on inductive signaling from the organizer or non-organizer regions will be evaluated, and potential molecular regulators of Zic3 in dorsal ectoderm will be characterized. Mutagenesis studies will be conducted to identify DNA regulatory elements of the Zic3 gene that respond to neural inducing signals. Currently existing models for anteroposterior neural tissue patterning will be experimentally tested in vivo and in vitro, by assessing specification of neuroectoderm at different times during gastrulation and the location of inducing signals responsible for anterior and posterior marker expression. A role of pre-existing polarity within ectoderm in anteroposterior neural patterning will be also evaluated. These experiments will shed more light on our knowledge of anteroposterior patterning of the vertebrate central nervous system.
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