Neocortical Expansion Due to Increased Proliferation of Basal Progenitors Is Linked to Changes in Their Morphology

Nereo Kalebic; Carlotta Gilardi; Barbara Stepien; Michaela Wilsch-Bräuninger; Katherine R. Long; Takashi Namba; Marta Florio; Barbara Langen; Benoit Lombardot; Anna Shevchenko; Manfred W. Kilimann; Hiroshi Kawasaki; Pauline Wimberger; Wieland B. Huttner

doi:10.1016/j.stem.2019.02.017

Neocortical Expansion Due to Increased Proliferation of Basal Progenitors Is Linked to Changes in Their Morphology

Nereo Kalebic, Carlotta Gilardi, Barbara Stepien, Michaela Wilsch-Bräuninger, Katherine R. Long, Takashi Namba, Marta Florio, Barbara Langen, Benoit Lombardot, Anna Shevchenko, Manfred W. Kilimann, Hiroshi Kawasaki, Pauline Wimberger, Wieland B. Huttner^*

^*Corresponding author for this work

Developmental Neurobiology

Research output: Contribution to journal › Article › peer-review

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Abstract

The evolutionary expansion of the mammalian neocortex (Ncx) is thought to be linked to increased proliferative capacity of basal progenitors (BPs) and their neurogenic capacity. Here, by quantifying BP morphology in the developing Ncx of mouse, ferret, and human, we show that increased BP proliferative capacity is linked to an increase in BP process number. We identify human membrane-bound PALMDELPHIN (PALMD-Caax) as an underlying factor, and we show that it drives BP process growth and proliferation when expressed in developing mouse and ferret Ncx. Conversely, CRISPR/Cas9-mediated disruption of PALMD or its binding partner ADDUCIN-γ in fetal human Ncx reduces BP process numbers and proliferation. We further show that PALMD-induced processes enable BPs to receive pro-proliferative integrin-dependent signals. These findings provide a link between BP morphology and proliferation, suggesting that changes in BP morphology may have contributed to the evolutionary expansion of the Ncx. Huttner and colleagues show that an increase in the number of neural progenitor cell processes underlies the proliferative capacity of this population. Expression of human membrane-bound PALMDELPHIN increases the number of progenitor processes and activates integrin signaling, leading to enhanced progenitor proliferation and an increase in upper-layer neurons.

Original language	English
Pages (from-to)	535-550.e9
Journal	Cell Stem Cell
Volume	24
Issue number	4
Early online date	21 Mar 2019
DOIs	https://doi.org/10.1016/j.stem.2019.02.017
Publication status	Published - 4 Apr 2019

Keywords

neocortical development
neocortical expansion
neural progenitor cells
neural progenitor morphology
Neurogenesis
Palmd

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Neocortical Expansion Due to Increased Proliferation_LONG_Publishedonline21March2019_GREEN AAMAccepted author manuscript, 11.1 MBLicence: CC BY-NC-ND

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Kalebic, N., Gilardi, C., Stepien, B., Wilsch-Bräuninger, M., Long, K. R., Namba, T., Florio, M., Langen, B., Lombardot, B., Shevchenko, A., Kilimann, M. W., Kawasaki, H., Wimberger, P., & Huttner, W. B. (2019). Neocortical Expansion Due to Increased Proliferation of Basal Progenitors Is Linked to Changes in Their Morphology. Cell Stem Cell, 24(4), 535-550.e9. https://doi.org/10.1016/j.stem.2019.02.017

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title = "Neocortical Expansion Due to Increased Proliferation of Basal Progenitors Is Linked to Changes in Their Morphology",

abstract = "The evolutionary expansion of the mammalian neocortex (Ncx) is thought to be linked to increased proliferative capacity of basal progenitors (BPs) and their neurogenic capacity. Here, by quantifying BP morphology in the developing Ncx of mouse, ferret, and human, we show that increased BP proliferative capacity is linked to an increase in BP process number. We identify human membrane-bound PALMDELPHIN (PALMD-Caax) as an underlying factor, and we show that it drives BP process growth and proliferation when expressed in developing mouse and ferret Ncx. Conversely, CRISPR/Cas9-mediated disruption of PALMD or its binding partner ADDUCIN-γ in fetal human Ncx reduces BP process numbers and proliferation. We further show that PALMD-induced processes enable BPs to receive pro-proliferative integrin-dependent signals. These findings provide a link between BP morphology and proliferation, suggesting that changes in BP morphology may have contributed to the evolutionary expansion of the Ncx. Huttner and colleagues show that an increase in the number of neural progenitor cell processes underlies the proliferative capacity of this population. Expression of human membrane-bound PALMDELPHIN increases the number of progenitor processes and activates integrin signaling, leading to enhanced progenitor proliferation and an increase in upper-layer neurons.",

keywords = "neocortical development, neocortical expansion, neural progenitor cells, neural progenitor morphology, Neurogenesis, Palmd",

author = "Nereo Kalebic and Carlotta Gilardi and Barbara Stepien and Michaela Wilsch-Br{\"a}uninger and Long, {Katherine R.} and Takashi Namba and Marta Florio and Barbara Langen and Benoit Lombardot and Anna Shevchenko and Kilimann, {Manfred W.} and Hiroshi Kawasaki and Pauline Wimberger and Huttner, {Wieland B.}",

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Kalebic, N, Gilardi, C, Stepien, B, Wilsch-Bräuninger, M, Long, KR, Namba, T, Florio, M, Langen, B, Lombardot, B, Shevchenko, A, Kilimann, MW, Kawasaki, H, Wimberger, P & Huttner, WB 2019, 'Neocortical Expansion Due to Increased Proliferation of Basal Progenitors Is Linked to Changes in Their Morphology', Cell Stem Cell, vol. 24, no. 4, pp. 535-550.e9. https://doi.org/10.1016/j.stem.2019.02.017

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T1 - Neocortical Expansion Due to Increased Proliferation of Basal Progenitors Is Linked to Changes in Their Morphology

AU - Kalebic, Nereo

AU - Gilardi, Carlotta

AU - Stepien, Barbara

AU - Wilsch-Bräuninger, Michaela

AU - Long, Katherine R.

AU - Namba, Takashi

AU - Florio, Marta

AU - Langen, Barbara

AU - Lombardot, Benoit

AU - Shevchenko, Anna

AU - Kilimann, Manfred W.

AU - Kawasaki, Hiroshi

AU - Wimberger, Pauline

AU - Huttner, Wieland B.

PY - 2019/4/4

Y1 - 2019/4/4

N2 - The evolutionary expansion of the mammalian neocortex (Ncx) is thought to be linked to increased proliferative capacity of basal progenitors (BPs) and their neurogenic capacity. Here, by quantifying BP morphology in the developing Ncx of mouse, ferret, and human, we show that increased BP proliferative capacity is linked to an increase in BP process number. We identify human membrane-bound PALMDELPHIN (PALMD-Caax) as an underlying factor, and we show that it drives BP process growth and proliferation when expressed in developing mouse and ferret Ncx. Conversely, CRISPR/Cas9-mediated disruption of PALMD or its binding partner ADDUCIN-γ in fetal human Ncx reduces BP process numbers and proliferation. We further show that PALMD-induced processes enable BPs to receive pro-proliferative integrin-dependent signals. These findings provide a link between BP morphology and proliferation, suggesting that changes in BP morphology may have contributed to the evolutionary expansion of the Ncx. Huttner and colleagues show that an increase in the number of neural progenitor cell processes underlies the proliferative capacity of this population. Expression of human membrane-bound PALMDELPHIN increases the number of progenitor processes and activates integrin signaling, leading to enhanced progenitor proliferation and an increase in upper-layer neurons.

AB - The evolutionary expansion of the mammalian neocortex (Ncx) is thought to be linked to increased proliferative capacity of basal progenitors (BPs) and their neurogenic capacity. Here, by quantifying BP morphology in the developing Ncx of mouse, ferret, and human, we show that increased BP proliferative capacity is linked to an increase in BP process number. We identify human membrane-bound PALMDELPHIN (PALMD-Caax) as an underlying factor, and we show that it drives BP process growth and proliferation when expressed in developing mouse and ferret Ncx. Conversely, CRISPR/Cas9-mediated disruption of PALMD or its binding partner ADDUCIN-γ in fetal human Ncx reduces BP process numbers and proliferation. We further show that PALMD-induced processes enable BPs to receive pro-proliferative integrin-dependent signals. These findings provide a link between BP morphology and proliferation, suggesting that changes in BP morphology may have contributed to the evolutionary expansion of the Ncx. Huttner and colleagues show that an increase in the number of neural progenitor cell processes underlies the proliferative capacity of this population. Expression of human membrane-bound PALMDELPHIN increases the number of progenitor processes and activates integrin signaling, leading to enhanced progenitor proliferation and an increase in upper-layer neurons.

KW - neocortical development

KW - neocortical expansion

KW - neural progenitor cells

KW - neural progenitor morphology

KW - Neurogenesis

KW - Palmd

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DO - 10.1016/j.stem.2019.02.017

M3 - Article

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AN - SCOPUS:85063715304

SN - 1934-5909

VL - 24

SP - 535-550.e9

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 4

ER -

Neocortical Expansion Due to Increased Proliferation of Basal Progenitors Is Linked to Changes in Their Morphology

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