From stem and progenitor cells to neurons in the developing neocortex: key differences among hominids

Mora-Bermúdez, Felipe; Taverna, Elena; Huttner, Wieland B.

doi:10.1111/febs.15793

“…This allows for a greater expansion of the NSPC pool, and of the subsequent neuronal progeny. This is consistent with the concept that the timing of developmental transitions, and the consequent total length of the neurogenic period, play major roles in determining the number of neurons produced by NSPCs and in the growth of the neocortex ( Rakic, 1995 , 2000 ; Lewitus et al, 2014 ; Stepien et al, 2020 ; Mora-Bermúdez et al, 2021 ). Further elucidating the cellular and molecular underpinnings of controlling the lengths of the proliferation phases and of the neurogenic period is likely to be very interesting.…”

Section: Temporal Differences In Neocortical Stem and Progenitor Cell...supporting

confidence: 90%

“…From these data, the key challenge emerges to compare the cellular and molecular features of human NSPCs with those of our closest non-extinct relatives, the non-human great apes ( Mora-Bermúdez et al, 2021 ). A huge advance toward this goal has been the development of the brain organoid technology ( Kadoshima et al, 2013 ; Lancaster et al, 2013 ; Pasca, 2018 ; Chiaradia and Lancaster, 2020 ; Velasco et al, 2020 ).…”

Section: Neocortical Stem and Progenitor Cell Types—are There Human-s...mentioning

confidence: 99%

What Are the Human-Specific Aspects of Neocortex Development?

Mora-Bermúdez

¹

,

Huttner

²

2022

Self Cite

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When considering what makes us human, the development of the neocortex, the seat of our higher cognitive abilities, is of central importance. Throughout this complex developmental process, neocortical stem and progenitor cells (NSPCs) exert a priming role in determining neocortical tissue fate, through a series of cellular and molecular events. In this Perspective article, we address five questions of relevance for potentially human-specific aspects of NSPCs, (i) Are there human-specific NSPC subtypes? (ii) What is the functional significance of the known temporal differences in NSPC dynamics between human and other great apes? (iii) Are there functional interactions between the human-specific genes preferentially expressed in NSPCs? (iv) Do humans amplify certain metabolic pathways for NSPC proliferation? and finally (v) Have differences evolved during human evolution, notably between modern humans and Neandertals, that affect the performance of key genes operating in NSPCs? We discuss potential implications inherent to these questions, and suggest experimental approaches on how to answer them, hoping to provide incentives to further understand key issues of human cortical development.

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“…Spindle genes experienced an unusually large number of missense changes in modern humans since the split from a common ancestor with archaic humans. This is intriguing, as mitotic metaphase has been shown to be prolonged in apical progenitors during human brain organoid development when compared to apes ( Mora-Bermúdez et al, 2016 ; Mora‐Bermúdez et al, 2021 ). Some of the missense changes in spindle genes that occurred since the separation of modern and archaic humans may be involved in such differences.…”

Section: Discussionmentioning

confidence: 99%

The evolutionary history of human spindle genes includes back-and-forth gene flow with Neandertals

Peyrégne

¹

,

Kelso

²

,

Peter

³

et al. 2022

eLife

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Proteins associated with the spindle apparatus, a cytoskeletal structure that ensures the proper segregation of chromosomes during cell division, experienced an unusual number of amino acid substitutions in modern humans after the split from the ancestors of Neandertals and Denisovans. Here, we analyze the history of these substitutions and show that some of the genes in which they occur may have been targets of positive selection. We also find that the two changes in the kinetochore scaffold 1 (KNL1) protein, previously believed to be specific to modern humans, were present in some Neandertals. We show that the KNL1 gene of these Neandertals shared a common ancestor with present-day Africans about 200,000 years ago due to gene flow from the ancestors (or relatives) of modern humans into Neandertals. Subsequently, some non-Africans inherited this modern human-like gene variant from Neandertals, but none inherited the ancestral gene variants. These results add to the growing evidence of early contacts between modern humans and archaic groups in Eurasia and illustrate the intricate relationships among these groups.

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“…Spindle genes experienced an unusually large number of missense changes in modern humans since the split from a common ancestor with archaic humans. This is intriguing, as mitotic metaphase has been shown to be prolonged in apical progenitors during human brain organoid development when compared to apes (39, 40). Some of the missense changes in spindle genes that occurred since the separation of modern and archaic humans may be involved in such differences.…”

Section: Discussionmentioning

confidence: 99%

The evolutionary history of human spindle genes includes back-and-forth gene flow with Neandertals

Peyrégne

¹

,

Kelso

²

,

Peter

³

et al. 2021

Preprint

1

0

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Proteins associated with the spindle apparatus, a cytoskeletal structure that ensures the proper segregation of chromosomes during cell division, experienced an unusual number of amino acid substitutions in modern humans after the split from the ancestors of Neandertals and Denisovans. Here, we analyze the history of these substitutions and show that some of the genes in which they occur may have been targets of positive selection. We also find that the two changes in the kinetochore scaffold 1 (KNL1) protein, previously believed to be specific to modern humans, were present in some Neandertals. We show that the KNL1 gene of these Neandertals shared a common ancestor with present-day Africans about 200,000 years ago due to gene flow from the ancestors (or relatives) of modern humans into Neandertals. Subsequently, some non-Africans inherited this modern human-like gene variant from Neandertals, but none inherited the ancestral gene variants. These results add to the growing evidence of early contacts between modern humans and archaic groups in Eurasia and illustrate the intricate relationships among these groups.

show abstract

From stem and progenitor cells to neurons in the developing neocortex: key differences among hominids

Cited by 12 publications

References 113 publications

What Are the Human-Specific Aspects of Neocortex Development?

What Are the Human-Specific Aspects of Neocortex Development?

The evolutionary history of human spindle genes includes back-and-forth gene flow with Neandertals

The evolutionary history of human spindle genes includes back-and-forth gene flow with Neandertals

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