Regulation of Gut and Heart Left–Right Asymmetry by Context-Dependent Interactions between Xenopus Lefty and BMP4 Signaling

Autor: Jeffrey J. Essner, William W. Branford, H. Joseph Yost
Rok vydání: 2000
Předmět:
Left-Right Determination Factors
Xenopus
Nodal
Nodal signaling
Bone Morphogenetic Protein 4
Xenopus Proteins
Mesoderm
Transforming Growth Factor beta
Morphogenesis
Paired Box Transcription Factors
Receptors
Interleukin-11
Heart looping
Embryonic Induction
Nuclear Proteins
Heart
Cell biology
medicine.anatomical_structure
Bone Morphogenetic Proteins
left–right axis
medicine.medical_specialty
animal structures
Lefty
Molecular Sequence Data
BMP4
Context (language use)
Pitx2
Biology
Models
Biological
TGFβ
Internal medicine
medicine
Animals
Interleukin-11 Receptor alpha Subunit
Amino Acid Sequence
intestine
Molecular Biology
Body Patterning
Glycoproteins
Homeodomain Proteins
Sequence Homology
Amino Acid
Lateral plate mesoderm
midline
Receptors
Interleukin
Cell Biology
Zebrafish Proteins
Endocrinology
Vg1
NODAL
Digestive System
Transcription Factors
Developmental Biology
Zdroj: Developmental Biology. 223:291-306
ISSN: 0012-1606
Popis: The Lefty subfamily of TGFbeta signaling molecules has been implicated in early development in mouse, zebrafish, and chick. Here, we show that Xenopus lefty (Xlefty) is expressed both bilaterally in symmetric midline domains and unilaterally in left lateral plate mesoderm and anterior dorsal endoderm. To examine the roles of Xlefty in left-right development, we created a system for scoring gut asymmetry and examined the effects of unilateral Xlefty misexpression on gut development, heart development, and Xnr-1 and XPitx2 expression. In contrast to the unilateral effects of Vg1, Activin, Nodal, or BMPs, targeted expression of Xlefty in either the left or the right side of Xenopus embryos randomized the direction of heart looping, gut coiling, and left-right positioning of the gut and downregulated the asymmetric expression of Xnr-1 and XPitx2. It is currently thought that Lefty proteins act as feedback inhibitors of Nodal signaling. However, this would not explain the effects of right-sided Xlefty misexpression. Here, we show that Xlefty interacts with the signaling pathways of other members of the TGFbeta family during left-right development. Results from coexpression of Xlefty and Vg1 indicate that Xlefty can nullify the effects of Vg1 ectopic expression and that Xlefty is downstream of left-sided Vg1 signaling. Results from coexpression of Xlefty and XBMP4 indicate that XLefty and XBMP4 interact both synergistically and antagonistically in a context-dependent manner. We propose a model in which interactions of Xlefty with multiple members of the TGFbeta family enhance the differences between the right-sided BMP/ALK2/Smad pathway and the left-sided Vg1/anti-BMP/Nodal pathway, leading to left-right morphogenesis of the gut and heart.
Databáze: OpenAIRE
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