Prof. Pete Scambler

Research Lead

Professor Pete Scambler

Contact us

Molecular Medicine Unit 
UCL Institute of Child Health 
30 Guilford Street
London WC1N 1EH 

Tel: +44 (0)20 7905 2635 

Congenital vascular defects

Congenital Vascular Defects - India ink injected into 10.5 day old mouse hearts. Ink seen tracking into three pharyngeal arch arteries (the fifth never forms in mice, and one and two have disappeared by this stage). Just one side of the embryo is shown. In embryos lacking one copy of Tbx1, a spectrum of severity of abnormality is seen in the fourth vessel: branches forming (B,C), thin vessels (D) or missing vessels (E).


Our research investigates the mechanisms underlying regulation of blood vessel Our work on vascular development springs from our understanding of defects underlying the DiGeorge and CHARGE syndromes, and investigations of the causative genes, Tbx1 and Chd7 respectively. In both cases, embryos lacking one of these genes have defects in the vasculature that derives from the paired pharyngeal arch arteries (PAAs). The pharyngeal arches are transitory segmented structures in the “neck” region of the mid-gestation embryo that give rise to many of the structures affected in the two syndromes. We know that the 4th pharyngeal arch artery is particularly important. The left 4th pharyngeal arch artery remodels to form part of the arch of the aorta, the main artery leaving the heart. Defects in this remodelling cause interruption of the aortic arch and create a condition incompatible with life (without surgical intervention). Other vascular defects seen in DiGeorge and CHARGE can be ascribed to abnormal modelling of the other arch arteries. Our aim is to identify the pathways that control arch artery formation and remodelling.

Key research activities

Identification of Tbx1 Target Genes

Tbx1 is a protein that controls which other genes are switched on or off, up or down, during development. Our aim is to identify the network of genes that are subject to Tbx1 control, as a subset of these will be vital for development of the heart and the blood vessels. This work involves using techniques that can examine the expression level of over 20,000 genes at any one time. We compare embryos lacking Tbx1 with those having both copies of Tbx1. We then test to see whether loss of any potential “target” of Tbx1 makes the malformations due to loss of one Tbx1 copy worse. These experiments therefore test for genetic interactions, and point the way to entire pathways involved in cardiovascular development. For instance, we have discovered a molecule, Smad7, which influences how the pharyngeal arch arteries “recover” from loss of Tbx1.