An early cell shape transition drives evolutionary expansion of the human forebrain

Benito-Kwiecinski, Silvia; Giandomenico, Stefano L.; Sutcliffe, Magdalena; Riis, Erlend S.; Freire-Pritchett, Paula; Kelava, Iva; Wunderlich, Stephanie; Martin, Ulrich; Wray, Gregory A.; McDole, Katie; Lancaster, Madeline A.

doi:10.1016/j.cell.2021.02.050

Cited by 193 publications

(157 citation statements)

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“…Despite the similarities, human apical progenitors (APs; the founders stem and progenitor cells of the brain) were reported to have a longer prometaphase-metaphase length and a higher proliferative capacity (Mora-Bermudez et al, 2016), suggesting a possible contribution to the increase in the human neocortex size. In line with these findings, a recent report suggests a higher proliferative capacity of human forebrain organoid APs compared to those of gorilla organoids (Benito-Kwiecinski et al, 2021). The human organoids were found to be bigger in size and showed expanded lumens in comparison to the gorilla organoids.…”

Section: Brain Evolution In a Dish Cerebral Organoids As A Model Systsupporting

confidence: 71%

“…By analyzing cerebral organoids of human, chimpanzee and macaque using scRNAseq and accessible chromatin profiling Kanton et al found a slower neuronal development in human organoids relative to primates. In addition, human and chimpanzee cells followed distinct cell states along progenitorto-neuron lineages, identified by a progression through stem cell states, progenitor cells of multiple brain regions including the forebrain, midbrain, hindbrain, and retina into differentiation Kanton et al, 2019;Pollen et al, 2019;Benito-Kwiecinski et al, 2021), neural progenitors (NPCs) (Otani et al, 2016), neurons via NPCs (Marchetto et al, 2019), and directly induced neurons (Schörnig et al, 2021). (Bottom) Observed neuronal phenotypes in the respective neuronal system and their uniqueness in either humans or non-human apes.…”

Section: Brain Evolution In a Dish Cerebral Organoids As A Model Systmentioning

confidence: 99%

“…FIGURE 1 | Summary of neuronal phenotypes observed in human and ape neuronal models. The figure shows the differentiation of induced pluripotent stem cells (iPSCs) into cerebral organoids(Mora-Bermudez et al, 2016;Kanton et al, 2019;Pollen et al, 2019;Benito-Kwiecinski et al, 2021), neural progenitors (NPCs)(Otani et al, 2016), neurons via NPCs(Marchetto et al, 2019), and directly induced neurons(Schörnig et al, 2021). (Bottom) Observed neuronal phenotypes in the respective neuronal system and their uniqueness in either humans or non-human apes.…”

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confidence: 99%

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A Closer Look to the Evolution of Neurons in Humans and Apes Using Stem-Cell-Derived Model Systems

Schörnig

Taverna

2021

Front. Cell Dev. Biol.

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The cellular, molecular and functional comparison of neurons from closely related species is crucial in evolutionary neurobiology. The access to living tissue and post-mortem brains of humans and non-human primates is limited and the state of the tissue might not allow recapitulating important species-specific differences. A valid alternative is offered by neurons derived from induced pluripotent stem cells (iPSCs) obtained from humans and non-human apes and primates. We will review herein the contribution of iPSCs-derived neuronal models to the field of evolutionary neurobiology, focusing on species-specific aspects of neuron’s cell biology and timing of maturation. In addition, we will discuss the use of iPSCs for the study of ancient human traits.

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Section: Brain Evolution In a Dish Cerebral Organoids As A Model Systsupporting

confidence: 71%

Section: Brain Evolution In a Dish Cerebral Organoids As A Model Systmentioning

confidence: 99%

mentioning

confidence: 99%

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A Closer Look to the Evolution of Neurons in Humans and Apes Using Stem-Cell-Derived Model Systems

Schörnig

Taverna

2021

Front. Cell Dev. Biol.

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“…Such subtle changes in neurogenesis length may not be easily recapitulated in vitro . Interestingly, timing differences at earlier stages of cortical development modeled in vitro between human and other great apes have been noted in a recent study ( Benito-Kwiecinski et al, 2021 ). In this system, neuroepithelial cells in human cerebral organoids delayed the switch to a more mature transition morphotype prior to the onset of neurogenesis compared with chimpanzee and gorilla.…”

Section: Role Of Neurogenic Period Length In Neocortex Expansion—expementioning

confidence: 68%

Length of the Neurogenic Period—A Key Determinant for the Generation of Upper-Layer Neurons During Neocortex Development and Evolution

Stepien

Vaid

Huttner

2021

Front. Cell Dev. Biol.

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The neocortex, a six-layer neuronal brain structure that arose during the evolution of, and is unique to, mammals, is the seat of higher order brain functions responsible for human cognitive abilities. Despite its recent evolutionary origin, it shows a striking variability in size and folding complexity even among closely related mammalian species. In most mammals, cortical neurogenesis occurs prenatally, and its length correlates with the length of gestation. The evolutionary expansion of the neocortex, notably in human, is associated with an increase in the number of neurons, particularly within its upper layers. Various mechanisms have been proposed and investigated to explain the evolutionary enlargement of the human neocortex, focussing in particular on changes pertaining to neural progenitor types and their division modes, driven in part by the emergence of human-specific genes with novel functions. These led to an amplification of the progenitor pool size, which affects the rate and timing of neuron production. In addition, in early theoretical studies, another mechanism of neocortex expansion was proposed—the lengthening of the neurogenic period. A critical role of neurogenic period length in determining neocortical neuron number was subsequently supported by mathematical modeling studies. Recently, we have provided experimental evidence in rodents directly supporting the mechanism of extending neurogenesis to specifically increase the number of upper-layer cortical neurons. Moreover, our study examined the relationship between cortical neurogenesis and gestation, linking the extension of the neurogenic period to the maternal environment. As the exact nature of factors promoting neurogenic period prolongation, as well as the generalization of this mechanism for evolutionary distinct lineages, remain elusive, the directions for future studies are outlined and discussed.

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“…Human PSC-derived brain organoids recapitulate both temporal and spatial components of the neocortical development. Cerebral organoids at days 10–15 after seeding show tight junctions at the apical side of the SOX2-positive neural rosettes reminiscent of NECs in the developing human brain ( Benito-Kwiecinski et al, 2021 ). At week 5 of differentiation, cortical organoids possess mitotic NECs that are later replaced by vRGs ( Subramanian et al, 2017 ).…”

Section: Major Populations Of Cortical Neural Stem Cells Can Be Foundmentioning

confidence: 99%

The Effects of Environmental Adversities on Human Neocortical Neurogenesis Modeled in Brain Organoids

Sarieva

Mayer

2021

Front. Mol. Biosci.

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Over the past decades, a growing body of evidence has demonstrated the impact of prenatal environmental adversity on the development of the human embryonic and fetal brain. Prenatal environmental adversity includes infectious agents, medication, and substances of use as well as inherently maternal factors, such as diabetes and stress. These adversities may cause long-lasting effects if occurring in sensitive time windows and, therefore, have high clinical relevance. However, our knowledge of their influence on specific cellular and molecular processes of in utero brain development remains scarce. This gap of knowledge can be partially explained by the restricted experimental access to the human embryonic and fetal brain and limited recapitulation of human-specific neurodevelopmental events in model organisms. In the past years, novel 3D human stem cell-based in vitro modeling systems, so-called brain organoids, have proven their applicability for modeling early events of human brain development in health and disease. Since their emergence, brain organoids have been successfully employed to study molecular mechanisms of Zika and Herpes simplex virus-associated microcephaly, as well as more subtle events happening upon maternal alcohol and nicotine consumption. These studies converge on pathological mechanisms targeting neural stem cells. In this review, we discuss how brain organoids have recently revealed commonalities and differences in the effects of environmental adversities on human neurogenesis. We highlight both the breakthroughs in understanding the molecular consequences of environmental exposures achieved using organoids as well as the on-going challenges in the field related to variability in protocols and a lack of benchmarking, which make cross-study comparisons difficult.

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An early cell shape transition drives evolutionary expansion of the human forebrain

Cited by 193 publications

References 100 publications

A Closer Look to the Evolution of Neurons in Humans and Apes Using Stem-Cell-Derived Model Systems

A Closer Look to the Evolution of Neurons in Humans and Apes Using Stem-Cell-Derived Model Systems

Length of the Neurogenic Period—A Key Determinant for the Generation of Upper-Layer Neurons During Neocortex Development and Evolution

The Effects of Environmental Adversities on Human Neocortical Neurogenesis Modeled in Brain Organoids

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