1Identification of genes differentially expressed in the embryonic pig cerebral cortex before and after appearance of gyration

<p>Abstract</p> <p>Background</p> <p>Mammalian evolution is characterized by a progressive expansion of the surface area of the cerebral cortex, an increase that is accompanied by gyration of the cortical surface. The mechanisms controlling this gyration process are not well characterized but mutational analyses indicate that genes involved in neuronal migration play an important function. Due to the lack of gyration of the rodent brain it is important to establish alternative models to examine brain development during the gyration process. The pig brain is gyrated and accordingly is a candidate alternative model.</p> <p>Findings</p> <p>In this study we have identified genes differentially expressed in the pig cerebral cortex before and after appearance of gyration. Pig cortical tissue from two time points in development representing a non-folded, lissencephalic, brain (embryonic day 60) and primary-folded, gyrencephalic, brain (embryonic day 80) were examined by whole genome expression microarray studies. 91 differentially expressed transcripts (fold change >3) were identified. 84 transcripts were annotated and encoding proteins involved in for example neuronal migration, calcium binding, and cytoskeletal structuring. Quantitative real-time PCR was used to confirm the regulation of a subset of the identified genes.</p> <p>Conclusion</p> <p>This study provides identification of genes which are differentially expressed in the pig cerebral cortex before and after appearance of brain gyration. The identified genes include novel candidate genes which could have functional importance for brain development.</p

Study of pallial neurogenesis in shark embryos and the evolutionary origin of the subventricular zone

The dorsal part of the developing telencephalon is one of the brain areas that has suffered most drastic changes throughout vertebrate evolution. Its evolutionary increase in complexity was thought to be partly achieved by the appearance of a new neurogenic niche in the embryonic subventricular zone (SVZ). Here, a new kind of amplifying progenitors (basal progenitors) expressing Tbr2, undergo a second round of divisions, which is believed to have contributed to the expansion of the neocortex. Accordingly, the existence of a pallial SVZ has been classically considered exclusive of mammals. However, the lack of studies in ancient vertebrates precludes any clear conclusion about the evolutionary origin of the SVZ and the neurogenic mechanisms that rule pallial development. In this work, we explore pallial neurogenesis in a basal vertebrate, the shark Scyliorhinus canicula, through the study of the expression patterns of several neurogenic markers. We found that apical progenitors and radial migration are present in sharks, and therefore, their presence must be highly conserved throughout evolution. Surprisingly, we detected a subventricular band of ScTbr2-expressing cells, some of which also expressed mitotic markers, indicating that the existence of basal progenitors should be considered an ancestral condition rather than a novelty of mammals or amniotes. Finally, we report that the transcriptional program for the specification of glutamatergic pallial cells (Pax6, Tbr2, NeuroD, Tbr1) is also present in sharks. However, the segregation of these markers into different cell types is not clear yet, which may be linked to the lack of layering in anamniotesThis work was supported by the Spanish Ministerio de Economía y Competitividad-FEDER (BFU2014-5863-1P)S

The origin of neocortex: Lessons from comparative embryology

The mammalian neocortex is the great achievement of cortical development and evolution. Its basic structure and parameters are remarkably uniform. With the exception of the primate primary visual cortex, all cortical areas in all mammals have a six-layered dorsal cortex with similar cell numbers within a unit column. This constant feature of the cortex is surprising considering the differences in the elaboration and proportions of infragranular and supragranular cell layers between species and between cortical areas. In contrast with mammals, avian and reptilian dorsal cortex contains only a fraction of the cell types found in mammals, mostly corresponding to infragranular layers (subplate, layers 5 and 6). We shall speculate on the possible evolutionary changes in the mammalian developmental program that may have delivered the additional neural complexity of the cerebral cortex. In this article we compare recent data on cell proliferation patterns, modes of radial and tangential neuronal migration, and construction sequence of the cortical plate in various species (turtle, chick, mouse, rat, macaque, and human). Work in macaque and mouse revealed that the infragranular (lower) and supragranular (upper) cell layers are produced in different mitotic compartments. The infragranular cells mostly originate from divisions of radial glia in the ventricular zone (VZ), while the supragranular cells are derived from symmetrical divisions of intermediate progenitor cells in the subventricular zone (SVZ). Comparisons of the germinal zones at different stages of cortical neurogenesis in macaque and mouse also revealed that macaque has a larger SVZ germinal area, which is correlated to the more elaborate supragranular layers. In chick and turtle, where the neuronal equivalents to the supragranular layers are absent, there is no defined SVZ in their dorsal cortex. This suggests that the SVZ in dorsal cortex is a specific mammalian trait. The elaboration of the dorsal cortical mitotic compartments with distinct gene expression patterns producing different classes of cortical neurons might have been a major driving force behind the increasing complexity of the mammalian cortex. © 2007 Elsevier Inc. All rights reserved

Examining the relationship between early axon growth and transcription factor expression in the developing cerebral cortex

The transcription factors Satb2 (special AT-rich sequence binding protein 2) and Ctip2 (COUP-TF interacting protein 2) have been shown to be required for callosal and corticospinal axon growth respectively from subtypes of cerebral cortex projection neurons. In this study we investigated early stages of directed axon growth in the embryonic mouse cerebral cortex, and studied the possible correlation with the expression of Satb2 and Ctip2. Electroporation of an EYFP-expressing plasmid at embryonic day13.5 to label developing projection neurons revealed that directed axon growth is first seen in radially migrating neurons in the intermediate zone (IZ), prior to migration into the cortical plate, as has been suggested previously. Onset of expression of SATB2 and CTIP2 was also observed in the IZ, correlating well with this stage of migration and initiation of axon growth. Immunohistochemical staining through embryonic and early postnatal development revealed a significant population of Satb2/Ctip2 co-expressing cells, while retrograde axon tracing from the corpus callosum at embryonic day18.5 back-labelled many neurons with bi-directional axon processes. However, through retrograde tracing and simultaneous immunohistochemical staining we show that these bi-directional processes do not correlate with Satb2/Ctip2 co-expression. Our work shows that although expression of these transcription factors correlates well with the appearance of directed axon growth during cortical development, the transcriptional code underlying the bi-directional axonal projections of early neocortical neurons is not likely to be the result of Satb2/Ctip2 co-expression. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society