Robo1 modulates proliferation and neurogenesis in the developing neocortex

Mason L. Yeh, Yuko Gonda, Mathilda T M Mommersteeg, Melissa Barber, Athena R. Ypsilanti, Carina Hanashima, John G. Parnavelas, William D. Andrews

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The elaborate cytoarchitecture of the mammalian neocortex requires the timely production of its constituent pyramidal neurons and interneurons and their disposition in appropriate layers. Numerous chemotropic factors present in the forebrain throughout cortical development play important roles in the orchestration of these events. The Roundabout (Robo) family of receptors and their ligands, the Slit proteins, are expressed in the developing forebrain, and are known to play important roles in the generation and migration of cortical interneurons. However, few studies have investigated their function(s) in the development of pyramidal cells. Here, we observed expression of Robo1 and Slit genes (Slit1, Slit2) in cells lining the telencephalic ventricles, and found significant increases in progenitor cells //// (basal and apical) at embryonic day (E)12.5 and E14.5 in the developing cortex of Robo1-/-, Slit1-/-, and Slit1-/-/Slit2-/-, but not in mice lacking the other Robo or Slit genes. Using layer-specific markers, we found that both early and late-born pyramidal neuron populations were significantly increased in the cortices of Robo1-/- mice at the end of corticogenesis (E18.5). The excess number of cortical pyramidal neurons generated prenatally appears to die in early postnatal life. The observed increase in pyramidal neurons was due to prolonged proliferative activity of their progenitors and not due to changes in cell cycle events. This finding, confirmed by in utero electroporation with Robo1 short hairpin RNA (shRNA) or control constructs into progenitors along the ventricular zone as well as in dissociated cortical cell cultures, points to a novel role for Robo1 in regulating the proliferation and generation of pyramidal neurons.

Original languageEnglish
Pages (from-to)5717-5731
Number of pages15
JournalJournal of Neuroscience
Volume34
Issue number16
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Pyramidal Cells
Neocortex
Neurogenesis
Interneurons
Prosencephalon
Telencephalon
Electroporation
Small Interfering RNA
Genes
Cell Cycle
Stem Cells
Cell Culture Techniques
Ligands
Population
Proteins

Keywords

  • Corticogenesis
  • Progenitors
  • Proliferation
  • Robo

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Yeh, M. L., Gonda, Y., Mommersteeg, M. T. M., Barber, M., Ypsilanti, A. R., Hanashima, C., ... Andrews, W. D. (2014). Robo1 modulates proliferation and neurogenesis in the developing neocortex. Journal of Neuroscience, 34(16), 5717-5731. https://doi.org/10.1523/JNEUROSCI.4256-13.2014

Robo1 modulates proliferation and neurogenesis in the developing neocortex. / Yeh, Mason L.; Gonda, Yuko; Mommersteeg, Mathilda T M; Barber, Melissa; Ypsilanti, Athena R.; Hanashima, Carina; Parnavelas, John G.; Andrews, William D.

In: Journal of Neuroscience, Vol. 34, No. 16, 2014, p. 5717-5731.

Research output: Contribution to journalArticle

Yeh, ML, Gonda, Y, Mommersteeg, MTM, Barber, M, Ypsilanti, AR, Hanashima, C, Parnavelas, JG & Andrews, WD 2014, 'Robo1 modulates proliferation and neurogenesis in the developing neocortex', Journal of Neuroscience, vol. 34, no. 16, pp. 5717-5731. https://doi.org/10.1523/JNEUROSCI.4256-13.2014
Yeh, Mason L. ; Gonda, Yuko ; Mommersteeg, Mathilda T M ; Barber, Melissa ; Ypsilanti, Athena R. ; Hanashima, Carina ; Parnavelas, John G. ; Andrews, William D. / Robo1 modulates proliferation and neurogenesis in the developing neocortex. In: Journal of Neuroscience. 2014 ; Vol. 34, No. 16. pp. 5717-5731.
@article{7e6c359526f847029d54767b66b479d2,
title = "Robo1 modulates proliferation and neurogenesis in the developing neocortex",
abstract = "The elaborate cytoarchitecture of the mammalian neocortex requires the timely production of its constituent pyramidal neurons and interneurons and their disposition in appropriate layers. Numerous chemotropic factors present in the forebrain throughout cortical development play important roles in the orchestration of these events. The Roundabout (Robo) family of receptors and their ligands, the Slit proteins, are expressed in the developing forebrain, and are known to play important roles in the generation and migration of cortical interneurons. However, few studies have investigated their function(s) in the development of pyramidal cells. Here, we observed expression of Robo1 and Slit genes (Slit1, Slit2) in cells lining the telencephalic ventricles, and found significant increases in progenitor cells //// (basal and apical) at embryonic day (E)12.5 and E14.5 in the developing cortex of Robo1-/-, Slit1-/-, and Slit1-/-/Slit2-/-, but not in mice lacking the other Robo or Slit genes. Using layer-specific markers, we found that both early and late-born pyramidal neuron populations were significantly increased in the cortices of Robo1-/- mice at the end of corticogenesis (E18.5). The excess number of cortical pyramidal neurons generated prenatally appears to die in early postnatal life. The observed increase in pyramidal neurons was due to prolonged proliferative activity of their progenitors and not due to changes in cell cycle events. This finding, confirmed by in utero electroporation with Robo1 short hairpin RNA (shRNA) or control constructs into progenitors along the ventricular zone as well as in dissociated cortical cell cultures, points to a novel role for Robo1 in regulating the proliferation and generation of pyramidal neurons.",
keywords = "Corticogenesis, Progenitors, Proliferation, Robo",
author = "Yeh, {Mason L.} and Yuko Gonda and Mommersteeg, {Mathilda T M} and Melissa Barber and Ypsilanti, {Athena R.} and Carina Hanashima and Parnavelas, {John G.} and Andrews, {William D.}",
year = "2014",
doi = "10.1523/JNEUROSCI.4256-13.2014",
language = "English",
volume = "34",
pages = "5717--5731",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "16",

}

TY - JOUR

T1 - Robo1 modulates proliferation and neurogenesis in the developing neocortex

AU - Yeh, Mason L.

AU - Gonda, Yuko

AU - Mommersteeg, Mathilda T M

AU - Barber, Melissa

AU - Ypsilanti, Athena R.

AU - Hanashima, Carina

AU - Parnavelas, John G.

AU - Andrews, William D.

PY - 2014

Y1 - 2014

N2 - The elaborate cytoarchitecture of the mammalian neocortex requires the timely production of its constituent pyramidal neurons and interneurons and their disposition in appropriate layers. Numerous chemotropic factors present in the forebrain throughout cortical development play important roles in the orchestration of these events. The Roundabout (Robo) family of receptors and their ligands, the Slit proteins, are expressed in the developing forebrain, and are known to play important roles in the generation and migration of cortical interneurons. However, few studies have investigated their function(s) in the development of pyramidal cells. Here, we observed expression of Robo1 and Slit genes (Slit1, Slit2) in cells lining the telencephalic ventricles, and found significant increases in progenitor cells //// (basal and apical) at embryonic day (E)12.5 and E14.5 in the developing cortex of Robo1-/-, Slit1-/-, and Slit1-/-/Slit2-/-, but not in mice lacking the other Robo or Slit genes. Using layer-specific markers, we found that both early and late-born pyramidal neuron populations were significantly increased in the cortices of Robo1-/- mice at the end of corticogenesis (E18.5). The excess number of cortical pyramidal neurons generated prenatally appears to die in early postnatal life. The observed increase in pyramidal neurons was due to prolonged proliferative activity of their progenitors and not due to changes in cell cycle events. This finding, confirmed by in utero electroporation with Robo1 short hairpin RNA (shRNA) or control constructs into progenitors along the ventricular zone as well as in dissociated cortical cell cultures, points to a novel role for Robo1 in regulating the proliferation and generation of pyramidal neurons.

AB - The elaborate cytoarchitecture of the mammalian neocortex requires the timely production of its constituent pyramidal neurons and interneurons and their disposition in appropriate layers. Numerous chemotropic factors present in the forebrain throughout cortical development play important roles in the orchestration of these events. The Roundabout (Robo) family of receptors and their ligands, the Slit proteins, are expressed in the developing forebrain, and are known to play important roles in the generation and migration of cortical interneurons. However, few studies have investigated their function(s) in the development of pyramidal cells. Here, we observed expression of Robo1 and Slit genes (Slit1, Slit2) in cells lining the telencephalic ventricles, and found significant increases in progenitor cells //// (basal and apical) at embryonic day (E)12.5 and E14.5 in the developing cortex of Robo1-/-, Slit1-/-, and Slit1-/-/Slit2-/-, but not in mice lacking the other Robo or Slit genes. Using layer-specific markers, we found that both early and late-born pyramidal neuron populations were significantly increased in the cortices of Robo1-/- mice at the end of corticogenesis (E18.5). The excess number of cortical pyramidal neurons generated prenatally appears to die in early postnatal life. The observed increase in pyramidal neurons was due to prolonged proliferative activity of their progenitors and not due to changes in cell cycle events. This finding, confirmed by in utero electroporation with Robo1 short hairpin RNA (shRNA) or control constructs into progenitors along the ventricular zone as well as in dissociated cortical cell cultures, points to a novel role for Robo1 in regulating the proliferation and generation of pyramidal neurons.

KW - Corticogenesis

KW - Progenitors

KW - Proliferation

KW - Robo

UR - http://www.scopus.com/inward/record.url?scp=84899493440&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899493440&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.4256-13.2014

DO - 10.1523/JNEUROSCI.4256-13.2014

M3 - Article

C2 - 24741061

AN - SCOPUS:84899493440

VL - 34

SP - 5717

EP - 5731

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 16

ER -