Reintroduction of the archaic variant of
            <i>NOVA1</i>
            in cortical organoids alters neurodevelopment

Trujillo, Cleber A.; Rice, Edward S.; Schaefer, Nathan K.; Chaim, Isaac A.; Wheeler, Emily C.; Madrigal, Assael; Buchanan, Justin; Preissl, Sebastian; Wang, Allen; Negraes, Priscilla D.; Szeto, Ryan A.; Herai, Roberto Hirochi; Huseynov, Alik; Ferraz, Mariana Sacrini Ayres; Borges, Fernando S.; Kihara, Alexandre Hiroaki; Byrne, Ashley; Marin, Maximillian G.; Vollmers, Christopher; Brooks, Angela N.; Lautz, Jonathan D.; Semendeferi, Katerina; Shapiro, Beth; Yeo, G; Smith, Stephen; Green, Edward; Muotri, Alysson R.

doi:10.1126/science.aax2537

Cited by 104 publications

(47 citation statements)

References 77 publications

(64 reference statements)

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“…Many issues are epistemological, including the fact that the cognition of extinct hominin species cannot be directly assessed and valid model organisms for these species are currently non-existent (cf. Breyl 2020;Michlich 2018: 7;Putt et al 2017: 1; but see Dannemann et al 2020;Trujillo et al 2021). Fortunately, however, the small number of previous experimental studies provide a valuable, albeit only fragmentary picture of how Palaeolithic-stone-tool-related behaviors are associated with modern brain and cognitive functioning.…”

Section: Previous Experimental Studiesmentioning

confidence: 99%

Cognitive performance and specific aspects of language processing are associated with Oldowan-like chert flaking and retouch

Gabrić¹,

Banda²,

Karavanić³

2021

Preprint

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A vast amount of literature suggests a co-evolutionary relationship between Palaeolithic stone toolmaking, and cognition and specifically language. However, empirical data remain limited to indirect findings of neurophysiological studies. Furthermore, most Oldowan studies have used chert and have not investigated retouch, even though quartz and lava were predominant raw materials during periods of chert unavailability, and even though chert was disproportionately more frequently used for retouch compared to other raw materials during periods of chert availability, at least in the Olduvai Gorge. The study recruited 13 young adults with no prior experience in knapping. Subjects were taught by an experienced knapper to produce quartz choppers and chert sidescrapers in either a verbal or gestural condition. Two raters rated on a 5-point scale the subjects’ performances on specific steps of the two stone toolmaking tasks. In a post-experimental interview, subjects stated which aspects of the tasks they preferred or disfavored. Subjects also performed on a neuropsychological battery encompassing visuospatial, executive functioning, and linguistic tasks. Given the small sample size, the results should be regarded as exploratory and preliminary. Our results are further limited to the early acquisition phase and may not reflect processes in modern experienced knappers. Descriptive data suggested better performance across all stone toolmaking variables in the verbal compared to gestural condition, but only flake quality on the sidescraper task was significantly different between groups. Analyses of the stone toolmaking variables suggested subjects perceived quartz and chert flaking very differently. Correlational and other analyses suggested that quartz chopper manufacture was not associated with cognitive performance. Conversely, chert flaking and retouch were strongly associated with visuospatial working memory, showing that subjects with a higher memory span produced better chert flakes and retouch. Retouch only was moderately associated with executive functioning measures, showing subjects who made fewer errors on the tasks were better on retouch. Specific aspects of chert flaking were also associated with verbal fluency performance, showing, among others, moderate and strong positive associations with the productivity and rate of production of syntactically transitive verbs on action fluency. Evolutionary implications can be drawn from our research only if we controversially assume similar results would have been obtained had we tested early hominins and not modern humans. Following this axiom, our results suggest that Oldowan hominins relied on modern-like visuospatial working memory during chert flaking and retouch, and, to a lesser degree, modern-like executive functioning during chert retouch. This is contrary to previous Oldowan studies suggesting no involvement of executive functioning during Oldowan-like flaking. Results from the linguistic tasks controversially suggest that some of the prerequisites for aspects of action language and syntactic transitivity (verb-object phrases) in modern humans were to some degree present in Oldowan hominin populations. Because Olduvai Gorge hominins readily incorporated chert for stone toolmaking in periods of chert availability, our results suggest that these cognitive capacities were phylogenetically not related to chert knapping. Finally, we propose that the quality of performance on Oldowan flaking and retouch may not reflect the full level of cognitive capacities of Oldowan populations. We provide the first direct evidence for an association between Palaeolithic stone toolmaking and cognitive performance in modern humans, while previous studies have inferred cognitive processes from neuroimaging data. We also provide the first direct evidence for an association between Palaeolithic stone toolmaking, and action language and simple syntactic transitivity in modern humans.

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Section: Previous Experimental Studiesmentioning

confidence: 99%

Cognitive performance and specific aspects of language processing are associated with Oldowan-like chert flaking and retouch

Gabrić¹,

Banda²,

Karavanić³

2021

Preprint

View full text Add to dashboard Cite

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“…A duplicative transposition in modern humans of the gene BOLA2 which is involved in iron metabolism has been described (Nuttle et al, 2016) in a region associated with autism but the functional consequences are unknown. A recent study introduced a modern human-specific amino acid substitution in the splice factor NOVA1 and suggested that it has drastic effects on the differentiation of brain organoids (Trujillo et al, 2021), an observation that warrants further study.…”

Section: Introductionmentioning

confidence: 99%

Reduced purine biosynthesis in humans after their divergence from Neandertals

Stepanova

Moczulska

Vacano

et al. 2021

eLife

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We analyze the metabolomes of humans, chimpanzees and macaques in muscle, kidney and three different regions of the brain. Whereas several compounds in amino acid metabolism occur at either higher or lower concentrations in humans than in the other primates, metabolites downstream of adenylosuccinate lyase, which catalyzes two reactions in purine synthesis, occur at lower concentrations in humans. This enzyme carries an amino acid substitution that is present in all humans today but absent in Neandertals. By introducing the modern human substitution into the genomes of mice, as well as the ancestral, Neandertal-like substitution into the genomes of human cells, we show that this amino acid substitution contributes to much or all of the reduction of de novo synthesis of purines in humans.

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“…Single-nucleus RNA-seq then revealed differences in cell-type proportions at one and 2 months of development and variations in gene splicing. Finally, NOVA1 Ar/Ar organoids had lower levels of pre-and postsynaptic proteins with less colocalized synaptic puncta likely resulting in reduced synchrony and increased variability based on observed firing rate and coefficient variation when evaluated by MEA (Trujillo et al, 2021).…”

Section: Extinct Ancestral Modelingmentioning

confidence: 98%

Unraveling Human Brain Development and Evolution Using Organoid Models

Fernandes

Klein

Marchetto

2021

Front. Cell Dev. Biol.

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Brain organoids are proving to be physiologically relevant models for studying human brain development in terms of temporal transcriptional signature recapitulation, dynamic cytoarchitectural development, and functional electrophysiological maturation. Several studies have employed brain organoid technologies to elucidate human-specific processes of brain development, gene expression, and cellular maturation by comparing human-derived brain organoids to those of non-human primates (NHPs). Brain organoids have been established from a variety of NHP pluripotent stem cell (PSC) lines and many protocols are now available for generating brain organoids capable of reproducibly representing specific brain region identities. Innumerous combinations of brain region specific organoids derived from different human and NHP PSCs, with CRISPR-Cas9 gene editing techniques and strategies to promote advanced stages of maturation, will successfully establish complex brain model systems for the accurate representation and elucidation of human brain development. Identified human-specific processes of brain development are likely vulnerable to dysregulation and could result in the identification of therapeutic targets or disease prevention strategies. Here, we discuss the potential of brain organoids to successfully model human-specific processes of brain development and explore current strategies for pinpointing these differences.

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Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment

Cited by 104 publications

References 77 publications

Cognitive performance and specific aspects of language processing are associated with Oldowan-like chert flaking and retouch

Cognitive performance and specific aspects of language processing are associated with Oldowan-like chert flaking and retouch

Reduced purine biosynthesis in humans after their divergence from Neandertals

Unraveling Human Brain Development and Evolution Using Organoid Models

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