Combinatorial transcriptional interaction within the cardiac neural crest: a pair of HANDs in heart formation

The cardiac neural crest cells migrate from the rostral dorsal neural folds and populate the branchial arches, which contribute directly to the cardiac-outflow structures. Although neural crest cell specification is associated with a number of morphogenic factors, little is understood about the mechanisms by which transcription factors actually implement the transcriptional programs that dictate cell migration and later the differentiation into the proper cell types within the great vessels and the heart. It is clear from genetic evidence that members of the paired box family and basic helix-loop-helix (bHLH) transcription factors from the twist family of proteins are expressed in and play an important function in cardiac neural crest specification and differentiation. Interestingly, both paired box and bHLH factors can function as dimers and, in the case of twist family bHLH factors, partner choice can clearly dictate a change in transcriptional program. The focus of this review is to consider what role the protein-protein interactions of these transcription factors may play in determining cardiac neural crest specification and differentiation, and how genetic alteration of transcription factor stoichiometry within the cell may reflect more than a simple null event.