Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis

S. R. Ferrón, E. J. Radford, A. Domingo-Muelas, I. Kleine, A. Ramme, D. Gray, I. Sandovici, M. Constancia, A. Ward, T. R. Menheniott, A. C. Ferguson-Smith

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Genomic imprinting is implicated in the control of gene dosage in neurogenic niches. Here we address the importance of Igf2 imprinting for murine adult neurogenesis in the subventricular zone (SVZ) and in the subgranular zone (SGZ) of the hippocampus in vivo. In the SVZ, paracrine IGF2 is a cerebrospinal fluid and endothelial-derived neurogenic factor requiring biallelic expression, with mutants having reduced activation of the stem cell pool and impaired olfactory bulb neurogenesis. In contrast, Igf2 is imprinted in the hippocampus acting as an autocrine factor expressed in neural stem cells (NSCs) solely from the paternal allele. Conditional mutagenesis of Igf2 in blood vessels confirms that endothelial-derived IGF2 contributes to NSC maintenance in SVZ but not in the SGZ, and that this is regulated by the biallelic expression of IGF2 in the vascular compartment. Our findings indicate that a regulatory decision to imprint or not is a functionally important mechanism of transcriptional dosage control in adult neurogenesis.

Original languageEnglish
Article number8265
Pages (from-to)1-12
Number of pages12
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 15 Sep 2015

Fingerprint

Genomic Imprinting
stem cells
Lateral Ventricles
Neurogenesis
Stem cells
hippocampus
mice
Neural Stem Cells
Blood Vessels
Hippocampus
cerebrospinal fluid
Cerebrospinal fluid
mutagenesis
dosage
Mutagenesis
bulbs
Gene Dosage
Olfactory Bulb
blood vessels
Blood vessels

Cite this

Ferrón, S. R., Radford, E. J., Domingo-Muelas, A., Kleine, I., Ramme, A., Gray, D., ... Ferguson-Smith, A. C. (2015). Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis. Nature Communications, 6, 1-12. [8265]. https://doi.org/10.1038/ncomms9265

Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis. / Ferrón, S. R.; Radford, E. J.; Domingo-Muelas, A.; Kleine, I.; Ramme, A.; Gray, D.; Sandovici, I.; Constancia, M.; Ward, A.; Menheniott, T. R.; Ferguson-Smith, A. C.

In: Nature Communications, Vol. 6, 8265, 15.09.2015, p. 1-12.

Research output: Contribution to journalArticle

Ferrón, SR, Radford, EJ, Domingo-Muelas, A, Kleine, I, Ramme, A, Gray, D, Sandovici, I, Constancia, M, Ward, A, Menheniott, TR & Ferguson-Smith, AC 2015, 'Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis', Nature Communications, vol. 6, 8265, pp. 1-12. https://doi.org/10.1038/ncomms9265
Ferrón, S. R. ; Radford, E. J. ; Domingo-Muelas, A. ; Kleine, I. ; Ramme, A. ; Gray, D. ; Sandovici, I. ; Constancia, M. ; Ward, A. ; Menheniott, T. R. ; Ferguson-Smith, A. C. / Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis. In: Nature Communications. 2015 ; Vol. 6. pp. 1-12.
@article{543a513344054a9898352ab1a08c1cad,
title = "Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis",
abstract = "Genomic imprinting is implicated in the control of gene dosage in neurogenic niches. Here we address the importance of Igf2 imprinting for murine adult neurogenesis in the subventricular zone (SVZ) and in the subgranular zone (SGZ) of the hippocampus in vivo. In the SVZ, paracrine IGF2 is a cerebrospinal fluid and endothelial-derived neurogenic factor requiring biallelic expression, with mutants having reduced activation of the stem cell pool and impaired olfactory bulb neurogenesis. In contrast, Igf2 is imprinted in the hippocampus acting as an autocrine factor expressed in neural stem cells (NSCs) solely from the paternal allele. Conditional mutagenesis of Igf2 in blood vessels confirms that endothelial-derived IGF2 contributes to NSC maintenance in SVZ but not in the SGZ, and that this is regulated by the biallelic expression of IGF2 in the vascular compartment. Our findings indicate that a regulatory decision to imprint or not is a functionally important mechanism of transcriptional dosage control in adult neurogenesis.",
author = "Ferr{\'o}n, {S. R.} and Radford, {E. J.} and A. Domingo-Muelas and I. Kleine and A. Ramme and D. Gray and I. Sandovici and M. Constancia and A. Ward and Menheniott, {T. R.} and Ferguson-Smith, {A. C.}",
year = "2015",
month = "9",
day = "15",
doi = "10.1038/ncomms9265",
language = "English",
volume = "6",
pages = "1--12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis

AU - Ferrón, S. R.

AU - Radford, E. J.

AU - Domingo-Muelas, A.

AU - Kleine, I.

AU - Ramme, A.

AU - Gray, D.

AU - Sandovici, I.

AU - Constancia, M.

AU - Ward, A.

AU - Menheniott, T. R.

AU - Ferguson-Smith, A. C.

PY - 2015/9/15

Y1 - 2015/9/15

N2 - Genomic imprinting is implicated in the control of gene dosage in neurogenic niches. Here we address the importance of Igf2 imprinting for murine adult neurogenesis in the subventricular zone (SVZ) and in the subgranular zone (SGZ) of the hippocampus in vivo. In the SVZ, paracrine IGF2 is a cerebrospinal fluid and endothelial-derived neurogenic factor requiring biallelic expression, with mutants having reduced activation of the stem cell pool and impaired olfactory bulb neurogenesis. In contrast, Igf2 is imprinted in the hippocampus acting as an autocrine factor expressed in neural stem cells (NSCs) solely from the paternal allele. Conditional mutagenesis of Igf2 in blood vessels confirms that endothelial-derived IGF2 contributes to NSC maintenance in SVZ but not in the SGZ, and that this is regulated by the biallelic expression of IGF2 in the vascular compartment. Our findings indicate that a regulatory decision to imprint or not is a functionally important mechanism of transcriptional dosage control in adult neurogenesis.

AB - Genomic imprinting is implicated in the control of gene dosage in neurogenic niches. Here we address the importance of Igf2 imprinting for murine adult neurogenesis in the subventricular zone (SVZ) and in the subgranular zone (SGZ) of the hippocampus in vivo. In the SVZ, paracrine IGF2 is a cerebrospinal fluid and endothelial-derived neurogenic factor requiring biallelic expression, with mutants having reduced activation of the stem cell pool and impaired olfactory bulb neurogenesis. In contrast, Igf2 is imprinted in the hippocampus acting as an autocrine factor expressed in neural stem cells (NSCs) solely from the paternal allele. Conditional mutagenesis of Igf2 in blood vessels confirms that endothelial-derived IGF2 contributes to NSC maintenance in SVZ but not in the SGZ, and that this is regulated by the biallelic expression of IGF2 in the vascular compartment. Our findings indicate that a regulatory decision to imprint or not is a functionally important mechanism of transcriptional dosage control in adult neurogenesis.

U2 - 10.1038/ncomms9265

DO - 10.1038/ncomms9265

M3 - Article

VL - 6

SP - 1

EP - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 8265

ER -