Jag1 Modulates an Oscillatory Dll1-Notch-Hes1 Signaling Module to Coordinate Growth and Fate of Pancreatic Progenitors

Research output: Contribution to journal › Journal article › Research › peer-review

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Jag1 Modulates an Oscillatory Dll1-Notch-Hes1 Signaling Module to Coordinate Growth and Fate of Pancreatic Progenitors. / Seymour, Philip Allan; Collin, Caitlin Alexis; Egeskov-Madsen, Anuska la Rosa; Jørgensen, Mette Christine; Shimojo, Hiromi; Imayoshi, Itaru; de Lichtenberg, Kristian Honnens; Kopan, Raphael; Kageyama, Ryoichiro; Serup, Palle.

In: Developmental Cell, Vol. 52, No. 6, 2020, p. 731-747.e8.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Seymour, PA, Collin, CA, Egeskov-Madsen, ALR, Jørgensen, MC, Shimojo, H, Imayoshi, I, de Lichtenberg, KH, Kopan, R, Kageyama, R & Serup, P 2020, 'Jag1 Modulates an Oscillatory Dll1-Notch-Hes1 Signaling Module to Coordinate Growth and Fate of Pancreatic Progenitors', Developmental Cell, vol. 52, no. 6, pp. 731-747.e8. https://doi.org/10.1016/j.devcel.2020.01.015

APA

Seymour, P. A., Collin, C. A., Egeskov-Madsen, A. L. R., Jørgensen, M. C., Shimojo, H., Imayoshi, I., de Lichtenberg, K. H., Kopan, R., Kageyama, R., & Serup, P. (2020). Jag1 Modulates an Oscillatory Dll1-Notch-Hes1 Signaling Module to Coordinate Growth and Fate of Pancreatic Progenitors. Developmental Cell, 52(6), 731-747.e8. https://doi.org/10.1016/j.devcel.2020.01.015

Vancouver

Seymour PA, Collin CA, Egeskov-Madsen ALR, Jørgensen MC, Shimojo H, Imayoshi I et al. Jag1 Modulates an Oscillatory Dll1-Notch-Hes1 Signaling Module to Coordinate Growth and Fate of Pancreatic Progenitors. Developmental Cell. 2020;52(6):731-747.e8. https://doi.org/10.1016/j.devcel.2020.01.015

Author

Seymour, Philip Allan ; Collin, Caitlin Alexis ; Egeskov-Madsen, Anuska la Rosa ; Jørgensen, Mette Christine ; Shimojo, Hiromi ; Imayoshi, Itaru ; de Lichtenberg, Kristian Honnens ; Kopan, Raphael ; Kageyama, Ryoichiro ; Serup, Palle. / Jag1 Modulates an Oscillatory Dll1-Notch-Hes1 Signaling Module to Coordinate Growth and Fate of Pancreatic Progenitors. In: Developmental Cell. 2020 ; Vol. 52, No. 6. pp. 731-747.e8.

Bibtex

@article{7945d302c529496a8d1b366c078bc615,
title = "Jag1 Modulates an Oscillatory Dll1-Notch-Hes1 Signaling Module to Coordinate Growth and Fate of Pancreatic Progenitors",
abstract = "Notch signaling controls proliferation of multipotent pancreatic progenitor cells (MPCs) and their segregation into bipotent progenitors (BPs) and unipotent pro-acinar cells (PACs). Here, we showed that fast ultradian oscillations of the ligand Dll1 and the transcriptional effector Hes1 were crucial for MPC expansion, and changes in Hes1 oscillation parameters were associated with selective adoption of BP or PAC fate. Conversely, Jag1, a uniformly expressed ligand, restrained MPC growth. However, when its expression later segregated to PACs, Jag1 became critical for the specification of all but the most proximal BPs, and BPs were entirely lost in Jag1; Dll1 double mutants. Anatomically, ductal morphogenesis and organ architecture are minimally perturbed in Jag1 mutants until later stages, when ductal remodeling fails, and signs of acinar-to-ductal metaplasia appear. Our study thus uncovers that oscillating Notch activity in the developing pancreas, modulated by Jag1, is required to coordinate MPC growth and fate.",
keywords = "cis-inhibition, development, Dll1, fate, Hes1, Jag1, Notch, oscillations, pancreas",
author = "Seymour, {Philip Allan} and Collin, {Caitlin Alexis} and Egeskov-Madsen, {Anuska la Rosa} and J{\o}rgensen, {Mette Christine} and Hiromi Shimojo and Itaru Imayoshi and {de Lichtenberg}, {Kristian Honnens} and Raphael Kopan and Ryoichiro Kageyama and Palle Serup",
year = "2020",
doi = "10.1016/j.devcel.2020.01.015",
language = "English",
volume = "52",
pages = "731--747.e8",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "6",

}

RIS

TY - JOUR

T1 - Jag1 Modulates an Oscillatory Dll1-Notch-Hes1 Signaling Module to Coordinate Growth and Fate of Pancreatic Progenitors

AU - Seymour, Philip Allan

AU - Collin, Caitlin Alexis

AU - Egeskov-Madsen, Anuska la Rosa

AU - Jørgensen, Mette Christine

AU - Shimojo, Hiromi

AU - Imayoshi, Itaru

AU - de Lichtenberg, Kristian Honnens

AU - Kopan, Raphael

AU - Kageyama, Ryoichiro

AU - Serup, Palle

PY - 2020

Y1 - 2020

N2 - Notch signaling controls proliferation of multipotent pancreatic progenitor cells (MPCs) and their segregation into bipotent progenitors (BPs) and unipotent pro-acinar cells (PACs). Here, we showed that fast ultradian oscillations of the ligand Dll1 and the transcriptional effector Hes1 were crucial for MPC expansion, and changes in Hes1 oscillation parameters were associated with selective adoption of BP or PAC fate. Conversely, Jag1, a uniformly expressed ligand, restrained MPC growth. However, when its expression later segregated to PACs, Jag1 became critical for the specification of all but the most proximal BPs, and BPs were entirely lost in Jag1; Dll1 double mutants. Anatomically, ductal morphogenesis and organ architecture are minimally perturbed in Jag1 mutants until later stages, when ductal remodeling fails, and signs of acinar-to-ductal metaplasia appear. Our study thus uncovers that oscillating Notch activity in the developing pancreas, modulated by Jag1, is required to coordinate MPC growth and fate.

AB - Notch signaling controls proliferation of multipotent pancreatic progenitor cells (MPCs) and their segregation into bipotent progenitors (BPs) and unipotent pro-acinar cells (PACs). Here, we showed that fast ultradian oscillations of the ligand Dll1 and the transcriptional effector Hes1 were crucial for MPC expansion, and changes in Hes1 oscillation parameters were associated with selective adoption of BP or PAC fate. Conversely, Jag1, a uniformly expressed ligand, restrained MPC growth. However, when its expression later segregated to PACs, Jag1 became critical for the specification of all but the most proximal BPs, and BPs were entirely lost in Jag1; Dll1 double mutants. Anatomically, ductal morphogenesis and organ architecture are minimally perturbed in Jag1 mutants until later stages, when ductal remodeling fails, and signs of acinar-to-ductal metaplasia appear. Our study thus uncovers that oscillating Notch activity in the developing pancreas, modulated by Jag1, is required to coordinate MPC growth and fate.

KW - cis-inhibition

KW - development

KW - Dll1

KW - fate

KW - Hes1

KW - Jag1

KW - Notch

KW - oscillations

KW - pancreas

U2 - 10.1016/j.devcel.2020.01.015

DO - 10.1016/j.devcel.2020.01.015

M3 - Journal article

C2 - 32059775

AN - SCOPUS:85081696073

VL - 52

SP - 731-747.e8

JO - Developmental Cell

JF - Developmental Cell

SN - 1534-5807

IS - 6

ER -

ID: 239912109