An expression and function analysis of the CXCR4/SDF-1 signalling axis during pituitary gland development

Jose Mario Gonzalez-Meljem; Sarah Ivins; Cynthia Lilian Andoniadou; Paul Le Tissier; Peter Scambler; Juan Pedro Martinez-Barbera

doi:10.1371/journal.pone.0280001

An expression and function analysis of the CXCR4/SDF-1 signalling axis during pituitary gland development

Jose Mario Gonzalez-Meljem^*, Sarah Ivins, Cynthia Lilian Andoniadou, Paul Le Tissier, Peter Scambler, Juan Pedro Martinez-Barbera^*

^*Corresponding author for this work

Centre for Craniofacial & Regenerative Biology

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

Abstract

The chemokine SDF-1 (CXCL12) and its receptor CXCR4 control several processes during embryonic development such as the regulation of stem cell proliferation, differentiation, and migration. However, the role of this pathway in the formation of the pituitary gland is not understood. We sought to characterise the expression patterns of CXCR4, SDF-1 and CXCR7 at different stages of pituitary gland development. Our expression profiling revealed that SDF-1 is expressed in progenitor-rich regions of the pituitary anterior lobe, that CXCR4 and CXCR7 have opposite expression domains and that CXCR4 expression is conserved between mice and human embryos. We then assessed the importance of this signalling pathway in the development and function of the murine pituitary gland through conditional deletion of CXCR4 in embryonic pituitary progenitors. Successful and specific ablation of CXCR4 expression in embryonic pituitary progenitors did not lead to observable embryonic nor postnatal defects but allowed the identification of stromal CXCR4+ cells not derived from HESX1+ progenitors. Further analysis of constitutive SDF-1, CXCR7 and CXCR4 mutants of the pathway indicates that CXCR4 expression in HESX1+ cells and their descendants is not essential for normal pituitary development in mice.

Original language	English
Article number	e0280001
Journal	PLoS ONE
Volume	18
Issue number	2 February
DOIs	https://doi.org/10.1371/journal.pone.0280001
Publication status	Published - Feb 2023

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@article{4dd8b457816141219fae3ffb9b1b29d3,

title = "An expression and function analysis of the CXCR4/SDF-1 signalling axis during pituitary gland development",

abstract = "The chemokine SDF-1 (CXCL12) and its receptor CXCR4 control several processes during embryonic development such as the regulation of stem cell proliferation, differentiation, and migration. However, the role of this pathway in the formation of the pituitary gland is not understood. We sought to characterise the expression patterns of CXCR4, SDF-1 and CXCR7 at different stages of pituitary gland development. Our expression profiling revealed that SDF-1 is expressed in progenitor-rich regions of the pituitary anterior lobe, that CXCR4 and CXCR7 have opposite expression domains and that CXCR4 expression is conserved between mice and human embryos. We then assessed the importance of this signalling pathway in the development and function of the murine pituitary gland through conditional deletion of CXCR4 in embryonic pituitary progenitors. Successful and specific ablation of CXCR4 expression in embryonic pituitary progenitors did not lead to observable embryonic nor postnatal defects but allowed the identification of stromal CXCR4+ cells not derived from HESX1+ progenitors. Further analysis of constitutive SDF-1, CXCR7 and CXCR4 mutants of the pathway indicates that CXCR4 expression in HESX1+ cells and their descendants is not essential for normal pituitary development in mice.",

author = "Gonzalez-Meljem, {Jose Mario} and Sarah Ivins and Andoniadou, {Cynthia Lilian} and {Le Tissier}, Paul and Peter Scambler and Martinez-Barbera, {Juan Pedro}",

note = "Funding Information: JPMB is funded by Cancer Research UK, Children{\textquoteright}s Cancer and Leukaemia Group (www.cclg.org.uk), Children with Cancer UK (www.childrenwithcancer.org.uk), The Brain Tumour Charity (SIGNAL and EVEREST) (www.thebraintumourcharity.org), Great Ormond Street Hospital Children{\textquoteright}s Charity (www.gosh.org), the Morgan Adams Foundation (www.morganadamsfoundation.org) and National Institute of Health Research Biomedical Research Centre at the Great Ormond Street Hospital for Children NHS Foundation Trust (www.gosh.nhs. uk), and the University College London. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: Copyright: {\textcopyright} 2023 Gonzalez-Meljem et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

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month = feb,

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journal = "PLoS ONE",

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AU - Gonzalez-Meljem, Jose Mario

AU - Ivins, Sarah

AU - Andoniadou, Cynthia Lilian

AU - Le Tissier, Paul

AU - Scambler, Peter

AU - Martinez-Barbera, Juan Pedro

N1 - Funding Information: JPMB is funded by Cancer Research UK, Children’s Cancer and Leukaemia Group (www.cclg.org.uk), Children with Cancer UK (www.childrenwithcancer.org.uk), The Brain Tumour Charity (SIGNAL and EVEREST) (www.thebraintumourcharity.org), Great Ormond Street Hospital Children’s Charity (www.gosh.org), the Morgan Adams Foundation (www.morganadamsfoundation.org) and National Institute of Health Research Biomedical Research Centre at the Great Ormond Street Hospital for Children NHS Foundation Trust (www.gosh.nhs. uk), and the University College London. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: Copyright: © 2023 Gonzalez-Meljem et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2023/2

Y1 - 2023/2

N2 - The chemokine SDF-1 (CXCL12) and its receptor CXCR4 control several processes during embryonic development such as the regulation of stem cell proliferation, differentiation, and migration. However, the role of this pathway in the formation of the pituitary gland is not understood. We sought to characterise the expression patterns of CXCR4, SDF-1 and CXCR7 at different stages of pituitary gland development. Our expression profiling revealed that SDF-1 is expressed in progenitor-rich regions of the pituitary anterior lobe, that CXCR4 and CXCR7 have opposite expression domains and that CXCR4 expression is conserved between mice and human embryos. We then assessed the importance of this signalling pathway in the development and function of the murine pituitary gland through conditional deletion of CXCR4 in embryonic pituitary progenitors. Successful and specific ablation of CXCR4 expression in embryonic pituitary progenitors did not lead to observable embryonic nor postnatal defects but allowed the identification of stromal CXCR4+ cells not derived from HESX1+ progenitors. Further analysis of constitutive SDF-1, CXCR7 and CXCR4 mutants of the pathway indicates that CXCR4 expression in HESX1+ cells and their descendants is not essential for normal pituitary development in mice.

AB - The chemokine SDF-1 (CXCL12) and its receptor CXCR4 control several processes during embryonic development such as the regulation of stem cell proliferation, differentiation, and migration. However, the role of this pathway in the formation of the pituitary gland is not understood. We sought to characterise the expression patterns of CXCR4, SDF-1 and CXCR7 at different stages of pituitary gland development. Our expression profiling revealed that SDF-1 is expressed in progenitor-rich regions of the pituitary anterior lobe, that CXCR4 and CXCR7 have opposite expression domains and that CXCR4 expression is conserved between mice and human embryos. We then assessed the importance of this signalling pathway in the development and function of the murine pituitary gland through conditional deletion of CXCR4 in embryonic pituitary progenitors. Successful and specific ablation of CXCR4 expression in embryonic pituitary progenitors did not lead to observable embryonic nor postnatal defects but allowed the identification of stromal CXCR4+ cells not derived from HESX1+ progenitors. Further analysis of constitutive SDF-1, CXCR7 and CXCR4 mutants of the pathway indicates that CXCR4 expression in HESX1+ cells and their descendants is not essential for normal pituitary development in mice.

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U2 - 10.1371/journal.pone.0280001

DO - 10.1371/journal.pone.0280001

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VL - 18

JO - PLoS ONE

JF - PLoS ONE

IS - 2 February

M1 - e0280001

ER -

An expression and function analysis of the CXCR4/SDF-1 signalling axis during pituitary gland development

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