Gli/Zic factors pattern the neural plate by defining domains of cell differentiation

Abstract

Three cell types differentiate in the early frog neural plate: neural crest at the lateral edges, floorplate at the midline and primary neurons in three bilateral stripes. Floorplate cells and ventral neurons are induced by Sonic hedgehog1,2 (Shh) and neural crest and dorsal neurons are induced by epidermal factors such as bone morphogenetic proteins (BMPs)3. Neurogenesis in a subset of cells within the stripes involves lateral inhibition4. However, the process by which pools of precursors are defined in stereotypic domains in response to inductive signals is unknown. Here we show that frog Zic2 encodes a zinc-finger transcription factor of the Gli superfamily which is expressed in stripes that alternate with those in which primary neurons differentiate and overlap the domains of floorplate and neural crest progenitors. Zic2 inhibits neurogenesis and induces neural crest differentiation. Conversely, Gli proteins are widely expressed, induce neurogenesis and inhibit neural crest differentiation. Zic2 is therefore a vertebrate pre-pattern gene, encoding anti-neurogenic and crest-inducing functions that counteract the neurogenic but not the floorplate-inducing activity of Gli proteins. We propose that the combined function of Gli/Zic genes responds to inductive signals and induces patterned neural cell differentiation.

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Figure 1: Neural expression of Zic2 in frog embryos.
Figure 2: Effects of Zic2 and VP16–Zic2 on neurogenesis.
Figure 3: Induction of neurogenesis by Glis and repression by EnR–Gli2 and Zic2.
Figure 4: Neural crest induction by Zic2 and repression by VP16–Zic2 and Gli2.

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Acknowledgements

We thank G. Fishell, R. Lehmann, M. Belvin, W. Talbot, N. Dahmane, A. Schier and M. Van Doren for comments; K. Zimmerman for Pax3; Q. Ma and D. Anderson for Ngnr1; D. Turner for the pCS2 series; D. Kessler for pCS2-EnR; D. Melton for NCAM; and J. Aruga and H. Sive for discussion. This work was supported by Skirball Institute start-up funds, a Basil O'Connor Award from the March of Dimes a Pew Fellowship and a grant from the NIH to A.R.A.

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Correspondence to A. Ruiz i Altaba.

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Brewster, R., Lee, J. & Altaba, A. Gli/Zic factors pattern the neural plate by defining domains of cell differentiation. Nature 393, 579–583 (1998). https://doi.org/10.1038/31242

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