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See article by Conway et al. [1] (pages 314–328) in this issue. In this issue of Cardiovascular Research the group of Conway presents convincing data showing that the phenotype of the Splotch Sp2H mouse is the result of a decrease in the absolute numbers of pre-migratory cardiac neural crest cells rather than to a malfunctioning of the cardiac neural crest cells. These observations touch upon the important question of whether the quality, i.e. neural crest origin or merely the quantity of the mesenchyme is important for proper outflow tract (OFT) septation [1]. During early development neural folds are formed along the anteroposterior-axis in the ectoderm. Upon fusion the folds give rise to the neural tube. During the process of neural tube formation, cells detach at the border of the neural and epidermal ectoderm, i.e. at the dorsal aspect of the forming neural tube. These cells are referred to as neural crest cells. Neural crest cells migrate along defined pathways throughout the body. Upon arrival at their destination, they differentiate into various cell types, among which melanocytes, peripheral neurons and their supporting cells, and skeletal elements. The neural crest cells are formed along the entire cranio–caudal axis of the body and can be divided into two major populations the cranial and truncal neural crest cells. The cranial neural crest extends from the diencephalon up to somite pair 5, and the truncal neural crest from somite pair 6 to the caudal end of the neural tube. The truncal neural crest is involved in sympathetic innervation of the heart, whereas the cranial neural crest is associated with parasympathetic innervation of the heart. The part of the cranial neural crest that extends from the mid-otic placode (or cleft between pharyngeal arch 2 and 3) to the level of somite pair 3 (or … * Corresponding author. University of Amsterdam, Department of Anatomy and Embryology, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. Tel.: +31-20-566-5378; fax: +31-20-697-6177 m.j.vandenhoff{at}amc.uva.nl