VanDusen, Nathan J.Vincentz, Joshua W.Firulli, Beth A.Howard, Marthe J.Rubart, MichaelFirulli, Anthony B.2016-02-192016-02-192014-04-15VanDusen, N. J., Vincentz, J. W., Firulli, B. A., Howard, M. J., Rubart, M., & Firulli, A. B. (2014). Loss of Hand2 in a population of Periostin lineage cells results in pronounced bradycardia and neonatal death. Developmental Biology, 388(2), 149–158. http://doi.org/10.1016/j.ydbio.2014.02.0100012-1606https://hdl.handle.net/1805/8381The Periostin Cre (Postn-Cre) lineage includes endocardial and neural crest derived mesenchymal cells of the cardiac cushions, neural crest-derived components of the sympathetic and enteric nervous systems, and cardiac fibroblasts. In this study, we use the Postn-Cre transgenic allele to conditionally ablate Hand2 (H2CKO). We find that Postn-Cre H2CKOs die shortly after birth despite a lack of obvious cardiac structural defects. To ascertain the cause of death, we performed a detailed comparison of the Postn-Cre lineage and Hand2 expression at mid and late stages of embryonic development. Gene expression analyses demonstrate that Postn-Cre ablates Hand2 from the adrenal medulla as well as the sphenopalatine ganglia of the head. In both cases, Hand2 loss-of-function dramatically reduces expression of Dopamine Beta Hydroxylase (Dbh), a gene encoding a crucial catecholaminergic biosynthetic enzyme. Expression of the genes Tyrosine Hydroxylase (Th) and Phenylethanolamine N-methyltransferase (Pnmt), which also encode essential catecholaminergic enzymes, were severely reduced in postnatal adrenal glands. Electrocardiograms demonstrate that 3-day postnatal Postn-Cre H2CKO pups exhibit sinus bradycardia. In conjunction with the aforementioned gene expression analyses, these results strongly suggest that the observed postnatal lethality occurs due to a catecholamine deficiency and subsequent heart failure.en-USPublisher PolicyBasic Helix-Loop-Helix Transcription FactorsphysiologyBradycardiaGeneticsHand2heart developmentsympathetic neurogenesisHeart FailureArticle