CRc are complex neuronal cells that develop early in the mammalian cortical MZ and undergo apoptotic degeneration near the end of cortical neuronal migration (Del Rio et al., 1996; Mienville, 1999; Frotscher et al., 2001; Grove and Fukuchi-Shimogori, 2003). They have multiple origins in telencephalic VZs and migrate in the PP by following several routes, particularly by tangential migration (Meyer and Wahle, 1999; Meyer et al., 2002; Takiguchi-Hayashi et al., 2004). In spite of heterogeneity of origin and migration pathways, mammalian CRc are uniquely characterized by a co-expression of reelin and the transcription factor p73, a member of the p53 family (Kaghad et al., 1997; Yang et al., 2000; Meyer et al., 2002) that may regulate their apoptosis.
As mentioned above, reelin-positive neurons are present in the early MZ in all amniotes, indicating, as a parsimonious hypothesis, that these cells may all be evolutionary-related and could have evolved from an ancestral CRc present in stem amniotes. On the other hand, the neuronal population of the embryonic MZ is more complex than previously thought (Meyer et al., 1998; Fairen et al., 2002), suggesting that the evolutionary history of CRc may be more intricate than such a simple evolutionary homology. Recently, co-expression of reelin and p73 was shown to be a defining feature of embryonic CRc in humans and rodents (Yang et al., 2000; Meyer et al., 2002). In order to assess whether CRc are indeed evolutionarily homologous, we studied reelin and p73 mRNA expression using double in situ hybridization with species-specific probes in the embryonic cortex of mice, turtles, lizards, crocodi-lians, and chicks.
As illustrated in Figure 4, early-born neurons in the embryonic cortical MZ in turtles and crocodiles co-express reelin and p73, as they do in mammals. The two probes label the same cells and single positive cells are rare. In turtles, the reelin-positive cells scattered in the CP are p73-negative. In crocodiles, the stream of reelin mRNA-expressing cells in the intermediate zone (Tissir et al., 2003) does not express p73 and thereby differs from MZ cells. Rather surprisingly, in chicks, despite the close similarity in terms of brain organization and evolutionary relationships with crocodiles, reelin and p73 are rarely co-expressed in MZ neurons. Similarly, in lizards, very few among the abundant reelin-positive MZ neurons are labeled with the p73 probes. There are several possible explanations to these findings, such as trivial problems in cloning and using p73 mRNA probes. p73 mRNA sequences are closely related to p53 and even more so to p63, and proved particularly difficult to clone in lizards. But, even with that restriction, the results at least show that expression of p73 is very low in chick and lizard and/or that reelin and p73 co-expression is rare in those species. The p73 gene is thought to regulate apoptosis and this regulation may be less important in reelin-positive subpial cells in chicks and lizards than in other species. If this is true, the co-expression of p73 and reelin may not be the best criterion to assess putative evolutionary homologies. Reelin-positive neurons are present in the developing brain of the lamprey (Perez-Costas et al., 2002), zebra fish, and Xenopus (Costagli et al., 2002), and the p73 gene was identified in zebra fish (Pan et al., 2003; Rentzsch et al., 2003). With the discovery of new molecular markers and the definition of more genomic sequences, tools should become available in the coming years to unravel the complex evolutionary history of MZ neurons.
Was this article helpful?