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Species-specific maturation profiles of human, chimpanzee and bonobo neural cells
https://elifesciences.org/articles/37527
https://elifesciences.org/articles/37527
Since the split from the last common ancestor of hominins (Homo) and African apes (Gorilla and Pan spp), human brain evolution has been characterized by several waves of increases in cranial capacity (Carlson et al., 2011; Falk et al., 2000) and selective expansion of regions implicated in complex cognition (Semendeferi et al., 2010; Semendeferi and Damasio, 2000). The increase in the cranial capacity in fossil hominins has been tied to behavioral changes, including the appearance of the first stone tools and their subsequent elaboration, increases in population size, and the spread of hominins into ecologically challenging habitats (Ambrose, 2001; Stout, 2011). Equally important were the subtle changes in brain organization at the microscopic level. While these changes cannot be inferred directly from the fossil specimens, comparative analyses of cortical organization between extant primate species suggest that the human brain indeed differs from the brain of other hominid species in several important microstructural aspects (Semendeferi et al., 2001; Barger et al., 2007; Semendeferi et al., 2011). One of these is the dendritic morphology of cortical pyramidal neurons, which differs between humans and the common chimpanzee (Pan troglodytes) (Bianchi et al., 2013a). Since cortical pyramidal neurons represent the most common type of neuron in the cortex and form basic units of cortical microcircuitry (DeFelipe and Fariñas, 1992), comparative analyses directed specifically at pyramidal neurons can yield insights into the organization of the microcircuitry that is typical of each species.
Differences observed in the adult phenotype between humans and chimpanzees likely reflect differences in timing and/or rate of cortical development. Developmental differences between species represent an important component in evolutionary studies, as small changes in the timing of development translate into morphological differences in adulthood, often with important functional implications. In the case of human brain evolution, sequential hypermorphosis, a type of heterochrony characterized by prolongation of all stages of brain development compared to the ancestral state (McNamara, 2002; Vrba, 1998; McKinney, 2002), has been proposed as an evolutionary mechanism underlying cerebral expansion in humans. Humans and apes share a pattern of prolonged postnatal growth in brain size that sets them apart from Old World monkeys (Leigh, 2004). Similarly, the maturation of pyramidal neurons appears to be protracted in hominids compared to macaques (Cupp and Uemura, 1980; Petanjek et al., 2011; Sedmak et al., 2018) and in humans compared to chimpanzees (Bianchi et al., 2013a; Teffer et al., 2013), possibly accounting for longer and more branched dendrites with higher numbers of dendritic spines in humans (Bianchi et al., 2013b; Petanjek et al., 2008). Because there is little evidence that the simple addition or subtraction of genes is sufficient to explain the observed differences (Hill and Walsh, 2005), changes in the regulation (levels and patterns of expression) of genes shared between humans and chimpanzees have been proposed to play an important role (King and Wilson, 1975; Enard et al., 2002). In particular, the expression of genes relevant to developmental events such as migration and dendritic maturation in pyramidal neurons can provide important insights into the underlying mechanisms shaping the differences in the organization of neuronal networks observed in humans and other primates.
Although studies using post-mortem brains from human and NHPs have provided important insights into developmental differences across species, the availability of specimens often limits the extent of the hypotheses that can be addressed. Recent advances in somatic reprogramming technology make comparative studies possible even in the absence of post-mortem specimens (Marchetto et al., 2013). The work presented here specifically addresses neural progenitor cell (NPC) migration and the development and functional maturation of cortical neurons in humans and chimpanzees. While changes in neural migration and cortical layering may pathologically affect early dendritic organization and microcircuitry formation in humans (Pramparo et al., 2015; Reiner et al., 2016; Muraki and Tanigaki, 2015; Brennand et al., 2015), previous research has not examined migration and early development of pyramidal neurons from an evolutionary perspective. We therefore hypothesized that the neurodevelopmental differences between humans and chimpanzees would become visible during distinct processes of NPC migration and during the initial establishment of the organization of dendritic trees and functional neuronal maturation in the neocortex. To test this hypothesis, we utilized induced pluripotent stem cell (iPSC) technology to model NPC migration in Homo and Pan spp. (chimpanzee and bonobo) and in the early development of cortical neurons.
We found differential migration patterns in human NPCs compared to those of chimpanzee and bonobo based on RNA expression profile analysis and live-cell imaging. Next, we observed morphological and functional developmental differences between human and chimpanzee neurons, suggesting differences in the timing of neuronal maturation between the two species. We report here in vitro and in vivo comparative analyses of the neural development of two closely related primate species. The strategy applied in this work can be utilized for further studies addressing human brain evolution and the mechanisms underlying the cellular and molecular aspects that are unique to the human brain.
Differences observed in the adult phenotype between humans and chimpanzees likely reflect differences in timing and/or rate of cortical development. Developmental differences between species represent an important component in evolutionary studies, as small changes in the timing of development translate into morphological differences in adulthood, often with important functional implications. In the case of human brain evolution, sequential hypermorphosis, a type of heterochrony characterized by prolongation of all stages of brain development compared to the ancestral state (McNamara, 2002; Vrba, 1998; McKinney, 2002), has been proposed as an evolutionary mechanism underlying cerebral expansion in humans. Humans and apes share a pattern of prolonged postnatal growth in brain size that sets them apart from Old World monkeys (Leigh, 2004). Similarly, the maturation of pyramidal neurons appears to be protracted in hominids compared to macaques (Cupp and Uemura, 1980; Petanjek et al., 2011; Sedmak et al., 2018) and in humans compared to chimpanzees (Bianchi et al., 2013a; Teffer et al., 2013), possibly accounting for longer and more branched dendrites with higher numbers of dendritic spines in humans (Bianchi et al., 2013b; Petanjek et al., 2008). Because there is little evidence that the simple addition or subtraction of genes is sufficient to explain the observed differences (Hill and Walsh, 2005), changes in the regulation (levels and patterns of expression) of genes shared between humans and chimpanzees have been proposed to play an important role (King and Wilson, 1975; Enard et al., 2002). In particular, the expression of genes relevant to developmental events such as migration and dendritic maturation in pyramidal neurons can provide important insights into the underlying mechanisms shaping the differences in the organization of neuronal networks observed in humans and other primates.
Although studies using post-mortem brains from human and NHPs have provided important insights into developmental differences across species, the availability of specimens often limits the extent of the hypotheses that can be addressed. Recent advances in somatic reprogramming technology make comparative studies possible even in the absence of post-mortem specimens (Marchetto et al., 2013). The work presented here specifically addresses neural progenitor cell (NPC) migration and the development and functional maturation of cortical neurons in humans and chimpanzees. While changes in neural migration and cortical layering may pathologically affect early dendritic organization and microcircuitry formation in humans (Pramparo et al., 2015; Reiner et al., 2016; Muraki and Tanigaki, 2015; Brennand et al., 2015), previous research has not examined migration and early development of pyramidal neurons from an evolutionary perspective. We therefore hypothesized that the neurodevelopmental differences between humans and chimpanzees would become visible during distinct processes of NPC migration and during the initial establishment of the organization of dendritic trees and functional neuronal maturation in the neocortex. To test this hypothesis, we utilized induced pluripotent stem cell (iPSC) technology to model NPC migration in Homo and Pan spp. (chimpanzee and bonobo) and in the early development of cortical neurons.
We found differential migration patterns in human NPCs compared to those of chimpanzee and bonobo based on RNA expression profile analysis and live-cell imaging. Next, we observed morphological and functional developmental differences between human and chimpanzee neurons, suggesting differences in the timing of neuronal maturation between the two species. We report here in vitro and in vivo comparative analyses of the neural development of two closely related primate species. The strategy applied in this work can be utilized for further studies addressing human brain evolution and the mechanisms underlying the cellular and molecular aspects that are unique to the human brain.
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