{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:38:19Z","timestamp":1790674699697,"version":"4.1.0"},"reference-count":47,"publisher":"The Company of Biologists","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,6,1]]},"abstract":"<jats:p>The regulation of neuronal survival and death by neurotrophic factors plays a central role in the sculpting of the nervous system, but the identity of survival signals for developing enteric neurons remains obscure. We demonstrate here that conditional ablation of GFR\u03b11,the high affinity receptor for GDNF, in mice during late gestation induces rapid and widespread neuronal death in the colon, leading to colon aganglionosis reminiscent of Hirschsprung's disease. Enteric neuron death induced by GFR\u03b11 inactivation is not associated with the activation of common cell death executors, caspase-3 or -7, and lacks the morphological hallmarks of apoptosis, such as chromatin compaction and mitochondrial pathology. Consistent with these in vivo observations, neither caspase inhibition nor Bax deficiency blocks death of colon-derived enteric neurons induced by GDNF deprivation. This study reveals an essential role for GFR\u03b11 in the survival of enteric neurons and suggests that caspase-independent death can be triggered by abolition of neurotrophic signals.<\/jats:p>","DOI":"10.1242\/dev.001388","type":"journal-article","created":{"date-parts":[[2007,5,16]],"date-time":"2007-05-16T17:29:30Z","timestamp":1179336570000},"page":"2171-2181","source":"Crossref","is-referenced-by-count":117,"title":["Conditional ablation of GFR\u03b11 in postmigratory enteric neurons triggers unconventional neuronal death in the colon and causes a Hirschsprung's disease phenotype"],"prefix":"10.1242","volume":"134","author":[{"given":"Toshihiro","family":"Uesaka","sequence":"first","affiliation":[{"name":"Laboratory for Neuronal Differentiation and Regeneration, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Jain","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Renal Division, Washington University School of Medicine, St Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigenobu","family":"Yonemura","sequence":"additional","affiliation":[{"name":"Laboratory for Cellular Morphogenesis, RIKEN Center for Developmental Biology,Kobe 650-0047, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Uchiyama","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neurosciences, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Milbrandt","sequence":"additional","affiliation":[{"name":"Pathology and Immunology, Washington University School of Medicine, St Louis,MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Enomoto","sequence":"additional","affiliation":[{"name":"Laboratory for Neuronal Differentiation and Regeneration, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042612394751100_REF1","doi-asserted-by":"crossref","unstructured":"Airaksinen, M. 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