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Published on: March 4, 2014
A vertebrate crossveinless 2 homologue modulates BMP activity and neural crest cell migration
Edward Coles1, Jeff Christiansen, Androulla Economou
1Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Abstract:
Previous work has revealed that proteins that bind to bone morphogenetic proteins (BMPs) and inhibit their signalling have a crucial role in the spatial and temporal regulation of cell differentiation and cell migration by BMPs. We have identified a chick homologue of crossveinless 2, a Drosophila gene that was identified in genetic studies as a promoter of BMP-like signalling. Chick Cv-2 has a conserved structure of five cysteine-rich repeats similar to those found in several BMP antagonists, and a C-terminal Von Willebrand type D domain. Cv-2 is expressed in the chick embryo in a number of tissues at sites at which elevated BMP signalling is required. One such site of expression is premigratory neural crest, in which at trunk levels threshold levels of BMP activity are required to initiate cell migration. We show that, when overexpressed, Cv-2 can weakly antagonise BMP4 activity in Xenopus embryos, but that in other in vitro assays Cv-2 can increase the activity of co-expressed BMP4. Furthermore, we find that increased expression of Cv-2 causes premature onset of trunk neural crest cell migration in the chick embryo, indicative of Cv-2 acting to promote BMP activity at an endogenous site of expression. We therefore propose that BMP signalling is modulated both by antagonists and by Cv-2 that acts to elevate BMP activity.
Insights
Chick crossveinless 2 (Cv-2) promotes bone morphogenetic protein (BMP) signaling, crucial for cell migration. This study identifies Cv-2
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Bone morphogenetic proteins (BMPs) regulate cell differentiation and migration.
- BMP signaling inhibitors play key roles in controlling these processes.
- The Drosophila gene crossveinless 2 (Cv-2) is known to promote BMP-like signaling.
Purpose of the Study:
- To identify and characterize a chick homologue of Drosophila crossveinless 2 (Cv-2).
- To investigate the role of chick Cv-2 in embryonic development, particularly in neural crest cell migration.
- To elucidate the mechanism by which Cv-2 modulates BMP signaling.
Main Methods:
- Identification and characterization of chick Cv-2 gene and protein structure.
- Analysis of Cv-2 expression patterns in chick embryos.
- Overexpression studies in Xenopus embryos to assess BMP4 antagonism/potentiation.
- In vitro assays to evaluate Cv-2's effect on BMP4 activity.
- In vivo studies in chick embryos to observe the effects of altered Cv-2 expression on neural crest cell migration.
Main Results:
- Chick Cv-2 shares structural similarities with known BMP antagonists but possesses a Von Willebrand type D domain.
- Cv-2 is expressed in chick embryos at sites requiring elevated BMP signaling, including premigratory neural crest.
- Overexpression of Cv-2 showed context-dependent effects, weakly antagonizing BMP4 in Xenopus but potentiating BMP4 activity in vitro.
- Increased Cv-2 expression in chick embryos led to premature trunk neural crest cell migration.
Conclusions:
- Chick Cv-2 acts to promote BMP activity at endogenous sites of expression, such as in the developing neural crest.
- Cv-2 plays a role in initiating trunk neural crest cell migration.
- BMP signaling is modulated by both antagonists and factors like Cv-2 that enhance BMP activity.
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