Monday, November 26, 2018 at 12:00pm to 1:00pm
Hedco Neurosciences Building (HNB), 100
3641 Watt Way, Los Angeles, CA 90089
Abstract: Mutations that disrupt the inwardly rectifying potassium channel Kir2.1 lead to Andersen-Tawil syndrome that includes periodic paralysis, cardiac arrhythmia, cognitive deficits, craniofacial dysmorphologies and limb defects. The molecular mechanism that underlies the developmental consequences of inhibition of these channels has remained a mystery. We show that Kir2.1 function is required in the cranial neural crest for morphogenesis of several craniofacial structures including palate closure in the mouse. We find that while the palatal shelves of Kir2.1-null embryos elevate properly, they are reduced in size due to decreased proliferation of the palatal mesenchyme. While we find no reduction in expression of BMP ligands, receptors, and associated Smads in this setting, loss of Kir2.1 reduces the efficacy of BMP signaling as shown by the reduction of phosphorylated Smad 1/5/8 and reduced expression of BMP targets Smad6 and Satb2. Our studies in fruit flies suggest that Kir channels regulate secretion of BMP.