RET overactivation leads to concurrent Hirschsprung disease and intestinal ganglioneuromas
Nandor Nagy, Richard A Guyer, Ryo Hotta, Dongcheng Zhang, Donald F Newgreen, Viktoria Halasy, Tamas Kovacs, Allan M Goldstein
Development | COMPANY BIOLOGISTS LTD | Published : 2020
Appropriately balanced RET signaling is of crucial importance during embryonic neural crest cell migration, proliferation and differentiation. RET deficiency, for example, leads to intestinal aganglionosis (Hirschsprung disease), whereas overactive RET can lead to multiple endocrine neoplasia (MEN) syndromes. Some RET mutations are associated with both intestinal aganglionosis and MEN-associated tumors. This seemingly paradoxical occurrence has led to speculation of a 'Janus mutation' in RET that causes overactivation or impairment of RET activity depending on the cellular context. Using an intestinal catenary culture system to test the effects of GDNF-mediated RET activation, we demonstrate..View full abstract
Awarded by National Institutes of Health
Awarded by Hungarian Science Foundation NKFI grant
A.M.G. is supported by the National Institutes of Health (R01DK103785, R01DK119210). N.N. is supported by a Bolyai Fellowship from the Magyar Tudoma ' nyos Akade ' mia, Excellence Program for Higher Education of Hungary (FIKP), and Hungarian Science Foundation NKFI grant (124740). R.A.G. is supported by the National Institutes of Health (F32DK121440). Deposited in PMC for release after 12 months.