Arteriovenous malformations (AVMs) are direct connections between arteries and veins that arise during active angiogenesis. Most AVMs are sporadic but some are associated with mutations in genes involved in TGFβ signalling. For example, mutations in activin receptor-like kinase 1 (ALK1, a TGFβ receptor) are implicated in the vascular disorder hereditary haemorrhagic telangiectasia 2 (HHT2). But what are the molecular and cellular errors that lead to AVM formation? On p. 1573 Beth Roman and colleagues address this question by analysing AVM development in alk1 mutant zebrafish embryos. They report that blood flow triggers alk1 expression in nascent arteries exposed to high haemodynamic forces and that Alk1 normally limits vessel calibre. In alk1 mutants, however, Alk1-dependent arteries are enlarged, and the downstream vessels adapt to the consequent increases in blood flow by retaining normally transient arteriovenous drainage connections, which subsequently enlarge to form AVMs. This two-step model for AVM formation suggests that HHT2 treatments might focus on preventing arterial enlargement and/or abrogating flow-induced AVM development.
Arteriovenous malformations go with the flow
Arteriovenous malformations go with the flow. Development 15 April 2011; 138 (8): e806. doi:
Download citation file:
Advertisement
Cited by
Biologists @ 100 - join us in Liverpool in March 2025

We are excited to invite you to a unique scientific conference, celebrating the 100-year anniversary of The Company of Biologists, and bringing together our different communities. The conference will incorporate the Spring Meetings of the BSCB and the BSDB, the JEB Symposium Sensory Perception in a Changing World and a DMM programme on antimicrobial resistance. Find out more and register by 28 February 2025 to join us in March 2025 in Liverpool, UK.
Call for papers – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues

Development invites you to submit your latest research to our upcoming special issue – Lifelong Development: the Maintenance, Regeneration and Plasticity of Tissues. This issue will be coordinated by Guest Editors Meritxell Huch (Max Planck Institute of Molecular Cell Biology and Genetics, Germany) and Mansi Srivastava (Harvard University and Museum of Comparative Zoology, USA), working alongside our team of academic Editors. Submit your articles by 15 May 2025.
A case for broadening our view of mechanism in developmental biology

In this Perspective, B. Duygu Özpolat and colleagues survey researchers on their views on what it takes to infer mechanism in developmental biology. They examine what factors shape our idea of what we mean by ‘mechanism’ and suggest a path forward that embraces a broad outlook on the diversity of studies that advance knowledge in our field.
In preprints
Did you know that Development publishes perspectives on recent preprints? These articles help our readers navigate the ever-growing preprint literature. We welcome proposals for ‘In preprints’ articles, so please do get in touch if you’d like to contribute.