Cerberus regulates left–right asymmetry of the embryonic head and heart
Autor: | Mark Mercola, Aaron Gardiner, Andrew B. Lassar, Martha J. Marvin, Michael Levin, Lei Zhu, Claudio D. Stern |
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Jazyk: | angličtina |
Předmět: |
Transcription
Genetic Chick Embryo Xenopus Proteins Mesoderm Xenopus laevis 0302 clinical medicine Transforming Growth Factor beta Chlorocebus aethiops Morphogenesis Paired Box Transcription Factors Sonic hedgehog 0303 health sciences Agricultural and Biological Sciences(all) biology PITX2 Wnt signaling pathway Gene Expression Regulation Developmental Nuclear Proteins Heart Cell biology Multigene Family Bone Morphogenetic Proteins COS Cells embryonic structures Intercellular Signaling Peptides and Proteins General Agricultural and Biological Sciences animal structures Nodal Protein Recombinant Fusion Proteins Molecular Sequence Data Transfection Bone morphogenetic protein General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Cerberus (protein) Species Specificity Animals Hedgehog Proteins Amino Acid Sequence Noggin Glycoproteins 030304 developmental biology Homeodomain Proteins Sequence Homology Amino Acid Biochemistry Genetics and Molecular Biology(all) Proteins Fibroblasts Molecular biology Gastrulation Trans-Activators biology.protein Carrier Proteins NODAL Head Sequence Alignment 030217 neurology & neurosurgery Transcription Factors |
Zdroj: | Current Biology. (17):931-938 |
ISSN: | 0960-9822 |
DOI: | 10.1016/S0960-9822(99)80419-9 |
Popis: | Background: Most of the molecules known to regulate left–right asymmetry in vertebrate embryos are expressed on the left side of the future trunk region of the embryo. Members of the protein family comprising Cerberus and the putative tumour suppressor Dan have not before been implicated in left–right asymmetry. In Xenopus , these proteins have been shown to antagonise members of the transforming growth factor β (TGF-β) and Wnt families of signalling proteins. Results: Chick Cerberus (cCer) was found to be expressed in the left head mesenchyme and in the left flank of the embryo. Expression on the left side of the head was controlled by Sonic hedgehog (Shh) acting through the TGF-β family member Nodal; in the flank, cCer was also regulated by Shh, but independently of Nodal. Surprisingly, although no known targets of Cerberus are expressed asymmetrically on the right side of the embryo at these stages, misexpression of cCer on this side of the embryo led to upregulation of the transcription factor Pitx2 and reversal of the direction of heart and head turning, apparently as independent events. Consistent with the possibility that cCer may be acting on bilaterally expressed TGF-β family members such as the bone morphogenetic proteins (BMPs), this result was mimicked by right-sided misexpression of the BMP antagonist, Noggin. Conclusions: Our findings suggest that cCer maintains a delicate balance of different TGF-β family members involved in laterality decisions, and reveal the existence of partially overlapping molecular pathways regulating left–right asymmetry in the head and trunk of the embryo. |
Databáze: | OpenAIRE |
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