Mind bomb 1 is required for pancreatic ß-cell formation

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Standard

Mind bomb 1 is required for pancreatic ß-cell formation. / Horn, Signe; Kobberup, Sune; Jørgensen, Mette C; Kalisz, Mark; Klein, Tino; Kageyama, Ryoichiro; Gegg, Moritz; Lickert, Heiko; Lindner, Jill; Magnuson, Mark A; Kong, Young-Yun; Serup, Palle; Ahnfelt-Rønne, Jonas; Jensen, Jan N.

I: Proceedings of the National Academy of Sciences USA (PNAS), Bind 109, Nr. 19, 08.05.2012, s. 7356-61.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Horn, S, Kobberup, S, Jørgensen, MC, Kalisz, M, Klein, T, Kageyama, R, Gegg, M, Lickert, H, Lindner, J, Magnuson, MA, Kong, Y-Y, Serup, P, Ahnfelt-Rønne, J & Jensen, JN 2012, 'Mind bomb 1 is required for pancreatic ß-cell formation', Proceedings of the National Academy of Sciences USA (PNAS), bind 109, nr. 19, s. 7356-61. https://doi.org/10.1073/pnas.1203605109

APA

Horn, S., Kobberup, S., Jørgensen, M. C., Kalisz, M., Klein, T., Kageyama, R., ... Jensen, J. N. (2012). Mind bomb 1 is required for pancreatic ß-cell formation. Proceedings of the National Academy of Sciences USA (PNAS), 109(19), 7356-61. https://doi.org/10.1073/pnas.1203605109

Vancouver

Horn S, Kobberup S, Jørgensen MC, Kalisz M, Klein T, Kageyama R o.a. Mind bomb 1 is required for pancreatic ß-cell formation. Proceedings of the National Academy of Sciences USA (PNAS). 2012 maj 8;109(19):7356-61. https://doi.org/10.1073/pnas.1203605109

Author

Horn, Signe ; Kobberup, Sune ; Jørgensen, Mette C ; Kalisz, Mark ; Klein, Tino ; Kageyama, Ryoichiro ; Gegg, Moritz ; Lickert, Heiko ; Lindner, Jill ; Magnuson, Mark A ; Kong, Young-Yun ; Serup, Palle ; Ahnfelt-Rønne, Jonas ; Jensen, Jan N. / Mind bomb 1 is required for pancreatic ß-cell formation. I: Proceedings of the National Academy of Sciences USA (PNAS). 2012 ; Bind 109, Nr. 19. s. 7356-61.

Bibtex

@article{36e3c4472e824e48bf481766ffb206b2,
title = "Mind bomb 1 is required for pancreatic {\ss}-cell formation",
abstract = "During early pancreatic development, Notch signaling represses differentiation of endocrine cells and promotes proliferation of Nkx6-1(+)Ptf1a(+) multipotent progenitor cells (MPCs). Later, antagonistic interactions between Nkx6 transcription factors and Ptf1a function to segregate MPCs into distal Nkx6-1(-)Ptf1a(+) acinar progenitors and proximal Nkx6-1(+)Ptf1a(-) duct and {\ss}-cell progenitors. Distal cells are initially multipotent, but evolve into unipotent, acinar cell progenitors. Conversely, proximal cells are bipotent and give rise to duct cells and late-born endocrine cells, including the insulin producing {\ss}-cells. However, signals that regulate proximodistal (P-D) patterning and thus formation of {\ss}-cell progenitors are unknown. Here we show that Mind bomb 1 (Mib1) is required for correct P-D patterning of the developing pancreas and {\ss}-cell formation. We found that endoderm-specific inactivation of Mib1 caused a loss of Nkx6-1(+)Ptf1a(-) and Hnf1{\ss}(+) cells and a corresponding loss of Neurog3(+) endocrine progenitors and {\ss}-cells. An accompanying increase in Nkx6-1(-)Ptf1a(+) and amylase(+) cells, occupying the proximal domain, suggests that proximal cells adopt a distal fate in the absence of Mib1 activity. Impeding Notch-mediated transcriptional activation by conditional expression of dominant negative Mastermind-like 1 (Maml1) resulted in a similarly distorted P-D patterning and suppressed {\ss}-cell formation, as did conditional inactivation of the Notch target gene Hes1. Our results reveal iterative use of Notch in pancreatic development to ensure correct P-D patterning and adequate {\ss}-cell formation.",
keywords = "Animals, Basic Helix-Loop-Helix Transcription Factors, Blotting, Western, Cell Lineage, Embryo, Mammalian, Female, Gene Expression Regulation, Developmental, Hepatocyte Nuclear Factor 1-beta, Hepatocyte Nuclear Factor 3-beta, Homeodomain Proteins, Insulin-Secreting Cells, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Mutation, Nerve Tissue Proteins, Nuclear Proteins, Pancreas, Receptors, Notch, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Time Factors, Transcription Factors, Ubiquitin-Protein Ligases",
author = "Signe Horn and Sune Kobberup and J{\o}rgensen, {Mette C} and Mark Kalisz and Tino Klein and Ryoichiro Kageyama and Moritz Gegg and Heiko Lickert and Jill Lindner and Magnuson, {Mark A} and Young-Yun Kong and Palle Serup and Jonas Ahnfelt-R{\o}nne and Jensen, {Jan N}",
year = "2012",
month = "5",
day = "8",
doi = "10.1073/pnas.1203605109",
language = "English",
volume = "109",
pages = "7356--61",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "19",

}

RIS

TY - JOUR

T1 - Mind bomb 1 is required for pancreatic ß-cell formation

AU - Horn, Signe

AU - Kobberup, Sune

AU - Jørgensen, Mette C

AU - Kalisz, Mark

AU - Klein, Tino

AU - Kageyama, Ryoichiro

AU - Gegg, Moritz

AU - Lickert, Heiko

AU - Lindner, Jill

AU - Magnuson, Mark A

AU - Kong, Young-Yun

AU - Serup, Palle

AU - Ahnfelt-Rønne, Jonas

AU - Jensen, Jan N

PY - 2012/5/8

Y1 - 2012/5/8

N2 - During early pancreatic development, Notch signaling represses differentiation of endocrine cells and promotes proliferation of Nkx6-1(+)Ptf1a(+) multipotent progenitor cells (MPCs). Later, antagonistic interactions between Nkx6 transcription factors and Ptf1a function to segregate MPCs into distal Nkx6-1(-)Ptf1a(+) acinar progenitors and proximal Nkx6-1(+)Ptf1a(-) duct and ß-cell progenitors. Distal cells are initially multipotent, but evolve into unipotent, acinar cell progenitors. Conversely, proximal cells are bipotent and give rise to duct cells and late-born endocrine cells, including the insulin producing ß-cells. However, signals that regulate proximodistal (P-D) patterning and thus formation of ß-cell progenitors are unknown. Here we show that Mind bomb 1 (Mib1) is required for correct P-D patterning of the developing pancreas and ß-cell formation. We found that endoderm-specific inactivation of Mib1 caused a loss of Nkx6-1(+)Ptf1a(-) and Hnf1ß(+) cells and a corresponding loss of Neurog3(+) endocrine progenitors and ß-cells. An accompanying increase in Nkx6-1(-)Ptf1a(+) and amylase(+) cells, occupying the proximal domain, suggests that proximal cells adopt a distal fate in the absence of Mib1 activity. Impeding Notch-mediated transcriptional activation by conditional expression of dominant negative Mastermind-like 1 (Maml1) resulted in a similarly distorted P-D patterning and suppressed ß-cell formation, as did conditional inactivation of the Notch target gene Hes1. Our results reveal iterative use of Notch in pancreatic development to ensure correct P-D patterning and adequate ß-cell formation.

AB - During early pancreatic development, Notch signaling represses differentiation of endocrine cells and promotes proliferation of Nkx6-1(+)Ptf1a(+) multipotent progenitor cells (MPCs). Later, antagonistic interactions between Nkx6 transcription factors and Ptf1a function to segregate MPCs into distal Nkx6-1(-)Ptf1a(+) acinar progenitors and proximal Nkx6-1(+)Ptf1a(-) duct and ß-cell progenitors. Distal cells are initially multipotent, but evolve into unipotent, acinar cell progenitors. Conversely, proximal cells are bipotent and give rise to duct cells and late-born endocrine cells, including the insulin producing ß-cells. However, signals that regulate proximodistal (P-D) patterning and thus formation of ß-cell progenitors are unknown. Here we show that Mind bomb 1 (Mib1) is required for correct P-D patterning of the developing pancreas and ß-cell formation. We found that endoderm-specific inactivation of Mib1 caused a loss of Nkx6-1(+)Ptf1a(-) and Hnf1ß(+) cells and a corresponding loss of Neurog3(+) endocrine progenitors and ß-cells. An accompanying increase in Nkx6-1(-)Ptf1a(+) and amylase(+) cells, occupying the proximal domain, suggests that proximal cells adopt a distal fate in the absence of Mib1 activity. Impeding Notch-mediated transcriptional activation by conditional expression of dominant negative Mastermind-like 1 (Maml1) resulted in a similarly distorted P-D patterning and suppressed ß-cell formation, as did conditional inactivation of the Notch target gene Hes1. Our results reveal iterative use of Notch in pancreatic development to ensure correct P-D patterning and adequate ß-cell formation.

KW - Animals

KW - Basic Helix-Loop-Helix Transcription Factors

KW - Blotting, Western

KW - Cell Lineage

KW - Embryo, Mammalian

KW - Female

KW - Gene Expression Regulation, Developmental

KW - Hepatocyte Nuclear Factor 1-beta

KW - Hepatocyte Nuclear Factor 3-beta

KW - Homeodomain Proteins

KW - Insulin-Secreting Cells

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Mice, Transgenic

KW - Mutation

KW - Nerve Tissue Proteins

KW - Nuclear Proteins

KW - Pancreas

KW - Receptors, Notch

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Signal Transduction

KW - Time Factors

KW - Transcription Factors

KW - Ubiquitin-Protein Ligases

U2 - 10.1073/pnas.1203605109

DO - 10.1073/pnas.1203605109

M3 - Journal article

VL - 109

SP - 7356

EP - 7361

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 19

ER -

ID: 42005114