1999
DOI: 10.1242/dev.126.12.2785
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Signalling by the RET receptor tyrosine kinase and its role in the development of the mammalian enteric nervous system

Abstract: RET is a member of the receptor tyrosine kinase (RTK) superfamily, which can transduce signalling by glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) in cultured cells. In order to determine whether in addition to being sufficient, RET is also necessary for signalling by these growth factors, we studied the response to GDNF and NTN of primary neuronal cultures (peripheral sensory and central dopaminergic neurons) derived from wild-type and RET-deficient mice. Our experiments show that abs… Show more

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Cited by 238 publications
(38 citation statements)
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“…Our findings show that pENCCs only expressing Ret 51 were capable of invading the mesenchyme of the proximal foregut but contrary to their Ret-deficient counterparts did not undergo apoptosis. These findings argue that signalling by Ret 51 is sufficient to support survival of ENCCs within the foregut thus bypassing the early apoptotic block in ENS development observed in Ret null mice (Taraviras et al, 1999). However, shortly after entering the foregut, ENS progenitors in Ret 51/51 mutants showed characteristic deficits in migration, proliferation and differentiation.…”
Section: Linage Tracing Of Neural Crest Cells Shows That Migration Is...mentioning
confidence: 86%
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“…Our findings show that pENCCs only expressing Ret 51 were capable of invading the mesenchyme of the proximal foregut but contrary to their Ret-deficient counterparts did not undergo apoptosis. These findings argue that signalling by Ret 51 is sufficient to support survival of ENCCs within the foregut thus bypassing the early apoptotic block in ENS development observed in Ret null mice (Taraviras et al, 1999). However, shortly after entering the foregut, ENS progenitors in Ret 51/51 mutants showed characteristic deficits in migration, proliferation and differentiation.…”
Section: Linage Tracing Of Neural Crest Cells Shows That Migration Is...mentioning
confidence: 86%
“…The critical role of the RTK Ret in the development of the mammalian ENS has been well established, and the cellular mechanisms controlled by this signalling pathway in vivo are becoming clearer (Lasrado et al, 2017;McCallum et al, 2020). The almost complete elimination of early ENS progenitors in Ret null mice (Taraviras et al, 1999) has precluded the analysis of the role of the receptor at later stages of enteric neurogenesis in vivo and much of our understanding of its role in ENS development so far has been explored using explant and cell culture assays. However, the role of Ret signalling in ENS development using a conditional Ret allele inactivated at relatively late stages of embryogenesis has been examined (Uesaka et al, 2007(Uesaka et al, , 2008Uesaka and Enomoto, 2010).…”
Section: Linage Tracing Of Neural Crest Cells Shows That Migration Is...mentioning
confidence: 99%
See 1 more Smart Citation
“…Ret gene encodes RET receptor tyrosine kinase that is activated by GDNF through the assembly of the receptor complexes with GFRα1 (Jing et al, 1996; Treanor et al, 1996). RET signaling is pleiotropic in ENS development, regulating (Natarajan et al, 2002; Uesaka et al, 2013; Young et al, 2001), proliferation (Gianino et al, 2003; Taraviras et al, 1999), neuronal differentiation (Uesaka et al, 2013), and survival (Taraviras et al, 1999; Uesaka et al, 2008) of vagal neural crest (NC)‐derived ENS progenitors. Mice that lack Gdnf , Gfrα1 , or Ret display a complete absence of enteric ganglia below stomach (Cacalano et al, 1998; Enomoto et al, 1998; Moore et al, 1996; Pichel et al, 1996; Sanchez et al, 1996; Schuchardt et al, 1994).…”
Section: Introductionmentioning
confidence: 99%
“…The enteric nervous system is derived from the vagal and sacral neural crest of somite levels 1–7 and 28 [6] . These crest cells give rise to enteric neurons and ganglia of the pre-umbilical and post-umbilical parts of the gut wall [7] .…”
Section: Origin and Development Of The Enteric Nervous Systemmentioning
confidence: 99%