Ptf1a-mediated control of Dll1 reveals an alternative to the lateral inhibition mechanism

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

Standard

Ptf1a-mediated control of Dll1 reveals an alternative to the lateral inhibition mechanism. / Jørgensen, Mette Christine; Ahnfelt-Rønne, Jonas; Klinck, Rasmus; Jensen, Jan N; Füchtbauer, Ernst-Martin; Deering, Tye; MacDonald, Raymond J; Wright, Chris V E; Madsen, Ole D; Serup, Palle.

In: Development, Vol. 139, No. 1, 01.2012, p. 33-45.

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

Harvard

Jørgensen, MC, Ahnfelt-Rønne, J, Klinck, R, Jensen, JN, Füchtbauer, E-M, Deering, T, MacDonald, RJ, Wright, CVE, Madsen, OD & Serup, P 2012, 'Ptf1a-mediated control of Dll1 reveals an alternative to the lateral inhibition mechanism', Development, vol. 139, no. 1, pp. 33-45. https://doi.org/10.1242/dev.071761

APA

Jørgensen, M. C., Ahnfelt-Rønne, J., Klinck, R., Jensen, J. N., Füchtbauer, E-M., Deering, T., MacDonald, R. J., Wright, C. V. E., Madsen, O. D., & Serup, P. (2012). Ptf1a-mediated control of Dll1 reveals an alternative to the lateral inhibition mechanism. Development, 139(1), 33-45. https://doi.org/10.1242/dev.071761

Vancouver

Jørgensen MC, Ahnfelt-Rønne J, Klinck R, Jensen JN, Füchtbauer E-M, Deering T et al. Ptf1a-mediated control of Dll1 reveals an alternative to the lateral inhibition mechanism. Development. 2012 Jan;139(1):33-45. https://doi.org/10.1242/dev.071761

Author

Jørgensen, Mette Christine ; Ahnfelt-Rønne, Jonas ; Klinck, Rasmus ; Jensen, Jan N ; Füchtbauer, Ernst-Martin ; Deering, Tye ; MacDonald, Raymond J ; Wright, Chris V E ; Madsen, Ole D ; Serup, Palle. / Ptf1a-mediated control of Dll1 reveals an alternative to the lateral inhibition mechanism. In: Development. 2012 ; Vol. 139, No. 1. pp. 33-45.

Bibtex

@article{c5e3dcb2c5d145ac92f5cf3371147fdb,
title = "Ptf1a-mediated control of Dll1 reveals an alternative to the lateral inhibition mechanism",
abstract = "Neurog3-induced Dll1 expression in pancreatic endocrine progenitors ostensibly activates Hes1 expression via Notch and thereby represses Neurog3 and endocrine differentiation in neighboring cells by lateral inhibition. Here we show in mouse that Dll1 and Hes1 expression deviate during regionalization of early endoderm, and later during early pancreas morphogenesis. At that time, Ptf1a activates Dll1 in multipotent pancreatic progenitor cells (MPCs), and Hes1 expression becomes Dll1 dependent over a brief time window. Moreover, Dll1, Hes1 and Dll1/Hes1 mutant phenotypes diverge during organ regionalization, become congruent at early bud stages, and then diverge again at late bud stages. Persistent pancreatic hypoplasia in Dll1 mutants after eliminating Neurog3 expression and endocrine development, together with reduced proliferation of MPCs in both Dll1 and Hes1 mutants, reveals that the hypoplasia is caused by a growth defect rather than by progenitor depletion. Unexpectedly, we find that Hes1 is required to sustain Ptf1a expression, and in turn Dll1 expression in early MPCs. Our results show that Ptf1a-induced Dll1 expression stimulates MPC proliferation and pancreatic growth by maintaining Hes1 expression and Ptf1a protein levels.",
keywords = "Animals, Basic Helix-Loop-Helix Transcription Factors, Bromodeoxyuridine, Chromatin Immunoprecipitation, Galactosides, Gene Expression Regulation, Homeodomain Proteins, Immunohistochemistry, Indoles, Intercellular Signaling Peptides and Proteins, Mice, Mice, Transgenic, Nerve Tissue Proteins, Pancreas, Pancreatic Polypeptide-Secreting Cells, Stem Cells, Transcription Factors",
author = "J{\o}rgensen, {Mette Christine} and Jonas Ahnfelt-R{\o}nne and Rasmus Klinck and Jensen, {Jan N} and Ernst-Martin F{\"u}chtbauer and Tye Deering and MacDonald, {Raymond J} and Wright, {Chris V E} and Madsen, {Ole D} and Palle Serup",
year = "2012",
month = jan,
doi = "10.1242/dev.071761",
language = "English",
volume = "139",
pages = "33--45",
journal = "Development",
issn = "0950-1991",
publisher = "The Company of Biologists",
number = "1",

}

RIS

TY - JOUR

T1 - Ptf1a-mediated control of Dll1 reveals an alternative to the lateral inhibition mechanism

AU - Jørgensen, Mette Christine

AU - Ahnfelt-Rønne, Jonas

AU - Klinck, Rasmus

AU - Jensen, Jan N

AU - Füchtbauer, Ernst-Martin

AU - Deering, Tye

AU - MacDonald, Raymond J

AU - Wright, Chris V E

AU - Madsen, Ole D

AU - Serup, Palle

PY - 2012/1

Y1 - 2012/1

N2 - Neurog3-induced Dll1 expression in pancreatic endocrine progenitors ostensibly activates Hes1 expression via Notch and thereby represses Neurog3 and endocrine differentiation in neighboring cells by lateral inhibition. Here we show in mouse that Dll1 and Hes1 expression deviate during regionalization of early endoderm, and later during early pancreas morphogenesis. At that time, Ptf1a activates Dll1 in multipotent pancreatic progenitor cells (MPCs), and Hes1 expression becomes Dll1 dependent over a brief time window. Moreover, Dll1, Hes1 and Dll1/Hes1 mutant phenotypes diverge during organ regionalization, become congruent at early bud stages, and then diverge again at late bud stages. Persistent pancreatic hypoplasia in Dll1 mutants after eliminating Neurog3 expression and endocrine development, together with reduced proliferation of MPCs in both Dll1 and Hes1 mutants, reveals that the hypoplasia is caused by a growth defect rather than by progenitor depletion. Unexpectedly, we find that Hes1 is required to sustain Ptf1a expression, and in turn Dll1 expression in early MPCs. Our results show that Ptf1a-induced Dll1 expression stimulates MPC proliferation and pancreatic growth by maintaining Hes1 expression and Ptf1a protein levels.

AB - Neurog3-induced Dll1 expression in pancreatic endocrine progenitors ostensibly activates Hes1 expression via Notch and thereby represses Neurog3 and endocrine differentiation in neighboring cells by lateral inhibition. Here we show in mouse that Dll1 and Hes1 expression deviate during regionalization of early endoderm, and later during early pancreas morphogenesis. At that time, Ptf1a activates Dll1 in multipotent pancreatic progenitor cells (MPCs), and Hes1 expression becomes Dll1 dependent over a brief time window. Moreover, Dll1, Hes1 and Dll1/Hes1 mutant phenotypes diverge during organ regionalization, become congruent at early bud stages, and then diverge again at late bud stages. Persistent pancreatic hypoplasia in Dll1 mutants after eliminating Neurog3 expression and endocrine development, together with reduced proliferation of MPCs in both Dll1 and Hes1 mutants, reveals that the hypoplasia is caused by a growth defect rather than by progenitor depletion. Unexpectedly, we find that Hes1 is required to sustain Ptf1a expression, and in turn Dll1 expression in early MPCs. Our results show that Ptf1a-induced Dll1 expression stimulates MPC proliferation and pancreatic growth by maintaining Hes1 expression and Ptf1a protein levels.

KW - Animals

KW - Basic Helix-Loop-Helix Transcription Factors

KW - Bromodeoxyuridine

KW - Chromatin Immunoprecipitation

KW - Galactosides

KW - Gene Expression Regulation

KW - Homeodomain Proteins

KW - Immunohistochemistry

KW - Indoles

KW - Intercellular Signaling Peptides and Proteins

KW - Mice

KW - Mice, Transgenic

KW - Nerve Tissue Proteins

KW - Pancreas

KW - Pancreatic Polypeptide-Secreting Cells

KW - Stem Cells

KW - Transcription Factors

U2 - 10.1242/dev.071761

DO - 10.1242/dev.071761

M3 - Journal article

C2 - 22096075

VL - 139

SP - 33

EP - 45

JO - Development

JF - Development

SN - 0950-1991

IS - 1

ER -

ID: 46483716