Mypt1-mediated spatial positioning of Bmp2-producing cells is essential for liver organogenesis.
Mesodermal tissues produce various inductive signals essential for morphogenesis of endodermal organs. However, little is known about how the spatial relationship between the mesodermal signal-producing cells and their target endodermal organs is established during morphogenesis. Here, we report that a mutation in the zebrafish myosin phosphatase targeting subunit 1 (mypt1) gene causes abnormal bundling of actin filaments and disorganization of lateral plate mesoderm (LPM) and endoderm cells. As a result, the coordination between mesoderm and endoderm cell movements is disrupted. Consequently, the two stripes of Bmp2a-expressing cells in the LPM fail to align in a V-shaped pocket sandwiching the liver primordium. Mispositioning Bmp2a-producing cells with respect to the liver primordium leads to a reduction in hepatoblast proliferation and final abortion of hepatoblasts by apoptosis, causing the liverless phenotype. Our results demonstrate that Mypt1 mediates coordination between mesoderm and endoderm cell movements in order to carefully position the liver primordium such that it receives a Bmp signal that is essential for liver formation in zebrafish.
Huang
Honghui
H
Laboratory of Functional Genomics, Institute of Molecular and Cell Biology, Proteos, Singapore.
Ruan
Hua
H
Aw
Meng Yuan
MY
Hussain
Alamgir
A
Guo
Lin
L
Gao
Chuan
C
Qian
Feng
F
Leung
Thomas
T
Song
Haiwei
H
Kimelman
David
D
Wen
Zilong
Z
Peng
Jinrong
J
D019943:Amino Acid Substitution; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis* / Q000235:genetics; D002465:Cell Movement; D049109:Cell Proliferation; D004247:DNA / Q000235:genetics; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D009154:Mutation; D043263:Myosin-Light-Chain Phosphatase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000096:biosynthesis* / Q000235:genetics
D055396:Bone Morphogenetic Protein 2; D029961:Zebrafish Proteins; D004247:DNA; D054645:Protein Phosphatase 1; D043263:Myosin-Light-Chain Phosphatase
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