2016-08-01
Regulators of gene expression in Enteric Neural Crest Cells are putative Hirschsprung disease genes
Publication
Publication
Developmental Biology , Volume 416 - Issue 1 p. 255- 265
The entericnervoussystem(ENS)isrequiredforperistalsisofthegutandisderivedfromEntericNeural Crest Cells(ENCCs).DuringENSdevelopment,theRETreceptortyrosinekinaseplaysacriticalroleinthe proliferationandsurvivalofENCCs,theirmigrationalongthedevelopinggut,anddifferentiationinto enteric neurons.Mutationsin RET and itsligand GDNF cause Hirschsprungdisease(HSCR),acomplex genetic disorderinwhichENCCsfailtocolonizevariablelengthsofthedistalbowel.Toidentifykey regulatorsofENCCsandthepathwaysunderlyingRETsignaling,geneexpressionprofiles ofuntreated and GDNF-treatedENCCsfromE14.5mouseembryosweregenerated.ENCCsexpressgenesthatare involvedinbothearlyandlateneuronaldevelopment,whereasGDNFtreatmentinducedneuronal maturation. PredictedregulatorsofgeneexpressioninENCCsincludetheknownHSCRgenes Ret and Sox10, aswellas Bdnf, App and Mapk10. Theregulatoryoverlapandfunctionalinteractionsbetweenthese genes wereusedtoconstructaregulatorynetworkthatisunderlyingENSdevelopmentandconnectsto known HSCRgenes.Inaddition,theadenosinereceptorA2a(Adora2a) andneuropeptideYreceptorY2 (Npy2r) wereidentified aspossibleregulatorsofterminalneuronaldifferentiationinGDNF-treated ENCCs. Thehumanorthologueof Npy2r maps totheHSCRsusceptibilitylocus4q31.3-q32.3,suggestinga role forNPY2RbothinENSdevelopmentandinHSCR.
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| doi.org/10.1016/j.ydbio.2016.06.004, hdl.handle.net/1765/96433 | |
| Developmental Biology | |
| Organisation | Department of Clinical Genetics |
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Schriemer, D. (Duco), Sribudiani, Y., IJpma, A., Natarajan, D., MacKenzie, K., Metzger, M., … Eggen, B. (2016). Regulators of gene expression in Enteric Neural Crest Cells are putative Hirschsprung disease genes. Developmental Biology, 416(1), 255–265. doi:10.1016/j.ydbio.2016.06.004 |
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