Cranial neural crest (CNC) cells are transient stem cells induced at the neural plate's border and migrate ventrally to produce most of the facial structures. They are induced by a combination of FGF, Wnt, and BMP4 signaling that are subtly modulated at the right position to define the neural crest territory. A Disintegrin and Metalloproteases (ADAMs) are transmembrane metalloproteases that have been shown to regulate signaling, adhesion, and cell migration in the CNC by proteolytically cleaving their many substrates. While the role of these proteases is well understood, a significant number of ADAMs do not have a catalytic active site and are, therefore, not proteases at all. Mechanistic studies concerning these non-proteolytic ADAM are lacking almost entirely. The cytoplasmic domain of ADAM10 has been shown to translocate into the nucleus following γ-secretase cleavage. Considering this, we can divide ADAM function into two categories, one dependent directly on proteolytic activity (Canonical ADAM function) and functions not directly dependent on proteolytic activity (Non-canonical function). In this thesis, we highlight the non-canonical function of ADAMs, by studying two ADAMs, Adam11 and Adam13. vii Adam11 is not a protease and has a very short cytoplasmic domain (11 amino acids), and Adam13 is a protease but has been previously shown to translocate to the nucleus and regulate gene expression. This study design lets us investigate two non-canonical aspects of ADAM function separately. In this thesis, we show that Adam11 is expressed within the CNC and binds to the BMP receptor BMR1A and Wnt receptor Frizzled7. We show that Adam11 positively regulates BMP4 signaling while negatively regulating β-catenin activity. Since the Adam11 cytoplasmic domain is unlikely to contribute to these functions, we next wanted to investigate the mechanism of ADAM cytoplasmic domain function. We show that Adam13 interacts with histone-modification enzymes and regulates histone modification in CNC. We also show that Adam13, along with Arid3a, regulates histone modifications at the promoter region of transcription factor Tfap2α. We show that Adam13 selectively promotes transcription of one variant of Tfap2α (Tfap2α-S1) while inhibiting another (Tfap2α-S3).