Cortical progenitor expansion, self-renewal and neurogenesis—a polarized perspective

Evolution of the mammalian neocortex (isocortex) has been a persisting problem in neurobiology. While recent studies have attempted to understand the evolutionary expansion of the human neocortex from rodents, similar approaches have been used to study the changes between reptiles, birds, and mammals. We review here findings from the past decades on the development, organization, and gene expression patterns in various extant species. This review aims to compare cortical cell numbers and neuronal cell types to the elaboration of progenitor populations and their proliferation in these species. Several progenitors, such as the ventricular radial glia, the subventricular intermediate progenitors, and the subventricular (outer) radial glia, have been identified but the contribution of each to cortical layers and cell types through specific lineages, their possible roles in determining brain size or cortical folding, are not yet understood. Across species, larger, more diverse progenitors relate to cortical size and cell diversity. The challenge is to relate the radial and tangential expansion of the neocortex to the changes in the proliferative compartments during mammalian evolution and with the changes in gene expression and lineages evident in various sectors of the developing brain. We also review the use of recent lineage tracing and transcriptomic approaches to revisit theories and to provide novel understanding of molecular processes involved in specification of cortical regions. J. Comp. Neurol. 524:630–645, 2016. © 2015 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Section: Does the Isocortex Of All Eutherian Mammals Develop From A Gmentioning

confidence: 99%

From sauropsids to mammals and back: New approaches to comparative cortical development

Montiel

Vasistha

García-Moreno

et al. 2015

“…The neocortex of these species is folded into grooves (sulci) and ridges (gyri), a trait known as gyrencephaly, as opposed to lissencephaly, in which the cortical surface is smooth (Lewitus et al, 2013; Zilles et al, 2013). To understand cortical expansion, it is necessary to study the developmental mechanisms underlying it, especially the roles played by the various types of neural progenitors with varying degrees of self‐renewing and neurogenic capacities and the processes that regulate their neuron output (Fietz and Huttner, 2011; Florio and Huttner, 2014; Franco and Muller, 2013; Kriegstein et al, 2006; Lewitus et al, 2013; Lui et al, 2011; Zilles et al, 2013). …”

mentioning

confidence: 99%

“…bRG are present in both lissencephalic and gyrencephalic species, normally in a much higher proportion in the latter (Fietz et al, 2010; Hansen et al, 2010; Kelava et al, 2012; Reillo et al, 2011; Shitamukai et al, 2011; Wang et al, 2011). They have been proposed to play a significant role in the development of gyrencephaly, both as a source of neurons and as a scaffolding element (Borrell and Reillo, 2012; Fietz and Huttner, 2011; Lui et al, 2011); however, their abundance alone does not account for the presence or absence of cortical folding (Kelava et al, 2012). …”

mentioning

confidence: 99%

S‐phase duration is the main target of cell cycle regulation in neural progenitors of developing ferret neocortex

García

Chang

Arai

et al. 2015

The evolutionary expansion of the neocortex primarily reflects increases in abundance and proliferative capacity of cortical progenitors and in the length of the neurogenic period during development. Cell cycle parameters of neocortical progenitors are an important determinant of cortical development. The ferret (Mustela putorius furo), a gyrencephalic mammal, has gained increasing importance as a model for studying corticogenesis. Here, we have studied the abundance, proliferation, and cell cycle parameters of different neural progenitor types, defined by their differential expression of the transcription factors Pax6 and Tbr2, in the various germinal zones of developing ferret neocortex. We focused our analyses on postnatal day 1, a late stage of cortical neurogenesis when upper‐layer neurons are produced. Based on cumulative 5‐ethynyl‐2′‐deoxyuridine (EdU) labeling as well as Ki67 and proliferating cell nuclear antigen (PCNA) immunofluorescence, we determined the duration of the various cell cycle phases of the different neocortical progenitor subpopulations. Ferret neocortical progenitors were found to exhibit longer cell cycles than those of rodents and little variation in the duration of G1 among distinct progenitor types, also in contrast to rodents. Remarkably, the main difference in cell cycle parameters among the various progenitor types was the duration of S‐phase, which became shorter as progenitors progressively changed transcription factor expression from patterns characteristic of self‐renewal to those of neuron production. Hence, S‐phase duration emerges as major target of cell cycle regulation in cortical progenitors of this gyrencephalic mammal. J. Comp. Neurol. 524:456–470, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

“…The enlarged supragranular layers of the primates arise from a specialized precursor pool, the outer subventricular zone (OSVZ) (Smart et al, 2002; Lukaszewicz et al, 2005). The OSVZ is the major germinal zone of the developing primate cerebral cortex and harbors the bulk of cortical progenitors from midcorticogenesis onward (Smart et al, 2002; Lukaszewicz et al, 2005; Fietz et al, 2010; Hansen et al, 2010; Fietz and Huttner, 2011; Lui et al, 2011; Reillo and Borrell, 2012; Betizeau et al, 2013). Although significant progress has been made in identifying the OSVZ precursor types in human (Hansen et al, 2010; Fietz and Huttner, 2011) and non‐human (Betizeau et al, 2013) primates, understanding the cellular and molecular properties of OSVZ precursors that drive its expansion in the primate lineage remains a major challenge (Lui et al, 2011; Dehay et al, 2015).…”

mentioning

confidence: 99%

“…bRGs were described as monopolar precursors with a basal process contacting the basal lamina, but lacking an apical process contacting the ventricle (Fietz et al, 2010; Hansen et al, 2010; Fietz and Huttner, 2011; Reillo and Borrell, 2012). A recent study in embryonic macaque, combining real‐time imaging of retrovirally infected green fluorescent protein (GFP)‐expressing progenitors from long‐term organotypic slice cultures with immunohistochemistry, showed that the bRG population is more diverse than previously reported in human studies (Betizeau et al, 2013).…”

mentioning

confidence: 99%

Unsupervised lineage‐based characterization of primate precursors reveals high proliferative and morphological diversity in the OSVZ

Pfeiffer

Betizeau

Waltispurger

et al. 2015

Generation of the primate cortex is characterized by the diversity of cortical precursors and the complexity of their lineage relationships. Recent studies have reported miscellaneous precursor types based on observer classification of cell biology features including morphology, stemness, and proliferative behavior. Here we use an unsupervised machine learning method for Hidden Markov Trees (HMTs), which can be applied to large datasets to classify precursors on the basis of morphology, cell‐cycle length, and behavior during mitosis. The unbiased lineage analysis automatically identifies cell types by applying a lineage‐based clustering and model‐learning algorithm to a macaque corticogenesis dataset. The algorithmic results validate previously reported observer classification of precursor types and show numerous advantages: It predicts a higher diversity of progenitors and numerous potential transitions between precursor types. The HMT model can be initialized to learn a user‐defined number of distinct classes of precursors. This makes it possible to 1) reveal as yet undetected precursor types in view of exploring the significant features of precursors with respect to specific cellular processes; and 2) explore specific lineage features. For example, most precursors in the experimental dataset exhibit bidirectional transitions. Constraining the directionality in the HMT model leads to a reduction in precursor diversity following multiple divisions, thereby suggesting that one impact of bidirectionality in corticogenesis is to maintain precursor diversity. In this way we show that unsupervised lineage analysis provides a valuable methodology for investigating fundamental features of corticogenesis. J. Comp. Neurol. 524:535–563, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.