Dickkopf1 Is Required for Embryonic Head Induction and Limb Morphogenesis in the Mouse

Mahua Mukhopadhyay; Svetlana Shtrom; Concepcion Rodriguez-Esteban; Lan Chen; Tohru Tsukui; Lauren Gomer; David W. Dorward; Andrei Glinka; Alexander Grinberg; Sing Ping Huang; Christof Niehrs; Juan Carlos Izpisúa Belmonte; Heiner Westphal

doi:10.1016/S1534-5807(01)00041-7

Dickkopf1 Is Required for Embryonic Head Induction and Limb Morphogenesis in the Mouse

Mahua Mukhopadhyay, Svetlana Shtrom, Concepcion Rodriguez-Esteban, Lan Chen, Tohru Tsukui, Lauren Gomer, David W. Dorward, Andrei Glinka, Alexander Grinberg, Sing Ping Huang, Christof Niehrs, Juan Carlos Izpisúa Belmonte, Heiner Westphal^*

^*Corresponding author for this work

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

546 Scopus citations

Abstract

Dickkopf1 (Dkk1) is a secreted protein that acts as a Wnt inhibitor and, together with BMP inhibitors, is able to induce the formation of ectopic heads in Xenopus. Here, we show that Dkk1 null mutant embryos lack head structures anterior of the midbrain. Analysis of chimeric embryos implicates the requirement of Dkk1 in anterior axial mesendoderm but not in anterior visceral endoderm for head induction. In addition, mutant embryos show duplications and fusions of limb digits. Characterization of the limb phenotype strongly suggests a role for Dkk1 both in cell proliferation and in programmed cell death. Our data provide direct genetic evidence for the requirement of secreted Wnt antagonists during embryonic patterning and implicate Dkk1 as an essential inducer during anterior specification as well as a regulator during distal limb patterning.

Original language	English (US)
Pages (from-to)	423-434
Number of pages	12
Journal	Developmental Cell
Volume	1
Issue number	3
DOIs	https://doi.org/10.1016/S1534-5807(01)00041-7
State	Published - Sep 2001
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
General Biochemistry, Genetics and Molecular Biology
Developmental Biology
Cell Biology

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10.1016/S1534-5807(01)00041-7

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title = "Dickkopf1 Is Required for Embryonic Head Induction and Limb Morphogenesis in the Mouse",

abstract = "Dickkopf1 (Dkk1) is a secreted protein that acts as a Wnt inhibitor and, together with BMP inhibitors, is able to induce the formation of ectopic heads in Xenopus. Here, we show that Dkk1 null mutant embryos lack head structures anterior of the midbrain. Analysis of chimeric embryos implicates the requirement of Dkk1 in anterior axial mesendoderm but not in anterior visceral endoderm for head induction. In addition, mutant embryos show duplications and fusions of limb digits. Characterization of the limb phenotype strongly suggests a role for Dkk1 both in cell proliferation and in programmed cell death. Our data provide direct genetic evidence for the requirement of secreted Wnt antagonists during embryonic patterning and implicate Dkk1 as an essential inducer during anterior specification as well as a regulator during distal limb patterning.",

author = "Mahua Mukhopadhyay and Svetlana Shtrom and Concepcion Rodriguez-Esteban and Lan Chen and Tohru Tsukui and Lauren Gomer and Dorward, {David W.} and Andrei Glinka and Alexander Grinberg and Huang, {Sing Ping} and Christof Niehrs and Belmonte, {Juan Carlos Izpis{\'u}a} and Heiner Westphal",

year = "2001",

month = sep,

doi = "10.1016/S1534-5807(01)00041-7",

language = "English (US)",

volume = "1",

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TY - JOUR

T1 - Dickkopf1 Is Required for Embryonic Head Induction and Limb Morphogenesis in the Mouse

AU - Mukhopadhyay, Mahua

AU - Shtrom, Svetlana

AU - Rodriguez-Esteban, Concepcion

AU - Chen, Lan

AU - Tsukui, Tohru

AU - Gomer, Lauren

AU - Dorward, David W.

AU - Glinka, Andrei

AU - Grinberg, Alexander

AU - Huang, Sing Ping

AU - Niehrs, Christof

AU - Belmonte, Juan Carlos Izpisúa

AU - Westphal, Heiner

PY - 2001/9

Y1 - 2001/9

N2 - Dickkopf1 (Dkk1) is a secreted protein that acts as a Wnt inhibitor and, together with BMP inhibitors, is able to induce the formation of ectopic heads in Xenopus. Here, we show that Dkk1 null mutant embryos lack head structures anterior of the midbrain. Analysis of chimeric embryos implicates the requirement of Dkk1 in anterior axial mesendoderm but not in anterior visceral endoderm for head induction. In addition, mutant embryos show duplications and fusions of limb digits. Characterization of the limb phenotype strongly suggests a role for Dkk1 both in cell proliferation and in programmed cell death. Our data provide direct genetic evidence for the requirement of secreted Wnt antagonists during embryonic patterning and implicate Dkk1 as an essential inducer during anterior specification as well as a regulator during distal limb patterning.

AB - Dickkopf1 (Dkk1) is a secreted protein that acts as a Wnt inhibitor and, together with BMP inhibitors, is able to induce the formation of ectopic heads in Xenopus. Here, we show that Dkk1 null mutant embryos lack head structures anterior of the midbrain. Analysis of chimeric embryos implicates the requirement of Dkk1 in anterior axial mesendoderm but not in anterior visceral endoderm for head induction. In addition, mutant embryos show duplications and fusions of limb digits. Characterization of the limb phenotype strongly suggests a role for Dkk1 both in cell proliferation and in programmed cell death. Our data provide direct genetic evidence for the requirement of secreted Wnt antagonists during embryonic patterning and implicate Dkk1 as an essential inducer during anterior specification as well as a regulator during distal limb patterning.

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U2 - 10.1016/S1534-5807(01)00041-7

DO - 10.1016/S1534-5807(01)00041-7

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AN - SCOPUS:18044399916

SN - 1534-5807

VL - 1

SP - 423

EP - 434

JO - Developmental Cell

JF - Developmental Cell

IS - 3

ER -

Dickkopf1 Is Required for Embryonic Head Induction and Limb Morphogenesis in the Mouse

Abstract

ASJC Scopus subject areas

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