Anti-Neural-Inhibition: A Conserved Mechanism for Neural Induction

While the previous discussion highlights the striking degree of evolutionary conservation in the mechanism for partitioning the ectoderm into neural versus nonneural components, it is not as clear that other aspects of D/V patterning have been conserved. For example, no vertebrate Dorsal-related gene has been implicated in early Xenopus development. Likewise, none of the identified maternally provided molecules in Xenopus thought to influence the position of the neural versus the nonneural ectoderm have been found to play a role in establishing D/V polarity in Drosophila. In Xenopus, the point of sperm entry in the animal hemisphere defines the opposing dorsal position of the Nieuwkoop center. Sperm entry triggers a cortical rotation and high levels of nuclear β-catenin in the Nieuwkoop center, perhaps by inhibiting the activity of Xgsk-3. High levels of nuclear β-catenin in the Nieuwkoop center trigger expression of the siamois homeobox gene, which is likely to act in combination with maternal signals such as Vg-1 and FGF to direct dorsal animal cells to form the neural-inducing Spemann organizer (for references, seeLarabell et al. 1997xLarabell, C.A, Torres, M, Rowning, B.A, Yost, C, Miller, J.R, Wu, M, Kimelman, D, and Moon, R.T. J. Cell Biol. 1997; 136: 1123–1136Crossref | PubMed | Scopus (302)See all ReferencesLarabell et al. 1997). As there are currently no identified maternal molecules controlling D/V patterning in common between Drosophila and Xenopus, it remains to be determined whether these earlier acting steps are based on diverse or conserved mechanisms.It also seems likely that there are organism-specific pathways involved in subdividing the ectoderm into neural versus nonneural components. For example, flies require a sensitized genetic background to reveal a role for Sog in blocking Dpp autoactivation in the neuroectoderm (Biehs et al. 1996xBiehs, B, Francois, V, and Bier, E. Genes Dev. 1996; 10: 2922–2934Crossref | PubMedSee all ReferencesBiehs et al. 1996). This suggests that another pathway collaborates with Sog to block Dpp expression in the neuroectoderm. Dorsal, which represses dpp expression in ventral and lateral cells, appears to be one factor acting in concert with Sog to block lateral dpp expression (Biehs et al. 1996xBiehs, B, Francois, V, and Bier, E. Genes Dev. 1996; 10: 2922–2934Crossref | PubMedSee all ReferencesBiehs et al. 1996), although it has not been resolved whether this is due to direct repression by Dorsal or results from activation of another Dpp antagonist. As no Dorsal-related protein has been implicated in vertebrate D/V patterning, the collaboration between Sog and Dorsal is most likely specific to flies or invertebrates. The observation that BMP-4 autoactivation can be triggered in dino single mutant zebrafish also is consistent with there being no equivalent maternal backup pathway in vertebrates.In frogs, there are other neuralizing factors in addition to Chd produced by the Spemann organizer such as Noggin, Follistatin, and Xnr3 (Xenopus nodal related 3), which block BMP-4 activity (for review, seeHemmati-Brivanlou and Melton 1997xHemmati-Brivanlou, A and Melton, D. Cell. 1997; 88: 13–17Abstract | Full Text | Full Text PDF | PubMedSee all ReferencesHemmati-Brivanlou and Melton 1997). Noggin functions like Chd to bind BMP-4 with high affinity. Also, FGF may play a role in posteriorizing neuroectoderm following its role in mesoderm formation. Although Xenopus Noggin can block Dpp signaling in flies (Holley et al. 1996xHolley, S.A, Neul, J.L, Attisano, L, Wrana, J.L, Sasai, Y, O'Connor, M.B, De Robertis, E.M, and Ferguson, E.L. Cell. 1996; 86: 607–617Abstract | Full Text | Full Text PDF | PubMed | Scopus (180)See all ReferencesHolley et al. 1996), there is as yet no evidence that there are fly homologs of noggin, follistatin, or nodal. A fly FGF has been isolated, but it does not play a role in neural development.Another potential difference between vertebrates and invertebrates is the mechanism by which neurogenesis is excluded from the mesoderm. In Drosophila, ventrally expressed Snail is responsible for repressing expression of neuroectodermal genes such as sog, rho, and AS-C genes in the mesoderm. While a Xenopus homolog of Snail has been identified, it is expressed too late to prevent mesodermal expression of early neural markers. In fact, the Spemann organizer, which expresses neural inducers such chd, noggin, and follistatin, is comprised principally of mesodermal cells that signal to the overlying ectoderm following involution. In Xenopus, the mesoderm is specified before neural induction and these cells most likely have lost the competence to respond to neural inducers by the time they are produced. Thus, there is no obviously conserved mechanism for defining neuroectodermal versus mesodermal cell fates.Future comparative analysis between vertebrates and invertebrates will be required to determine the extent to which conserved versus organism-specific pathways guide the first zygotic step of neurogenesis. In this regard, it is instructive to consider the great nineteenth century insights into development and evolution deduced from comparative studies of anatomy and development. It seems that the time is ripe to revisit this approach using the modern tools of molecular genetics.