13-P093 Defects in gut and enteric nervous system development in talpid3 mutant chicken

Alan Burns, Lucy Bradshaw, Megan Davey, Nikhil Thapar

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

The talpid3 chicken mutant has a wide range of phenotypic defects including paddle-shaped limbs, and face, skeleton and vascular abnormalities that result from defective Hedgehog (Hh) signalling. Since the Hh signalling pathway has been implicated in the development of the gastrointestinal tract and enteric nervous system (ENS), our aim was to examine talpid3 mutant embryos to gain further insight into the role of the Hh pathway in the development of these tissues. Macroscopically, the gut of talpid3 embryos was normally patterned along its length (esophagus, stomach, pre-umbilical intestine, post-umbilical intestine, hindgut), but overall it was significantly shorter compared with controls. In talpid3 gut, although neural crest-derived ENS precursors (shown with HNK-1 immunohistochemistry) and TuJ1-positive enteric neurons were distributed along the length of the gut, similar to controls, there were dramatic differences in their patterning across the gut wall. Also, the organisation of smooth muscle actin (SMA) was considerably altered in talpid3 mutants, with SMA staining absent in the esophagus, but distributed across the entire wall of the intestine. Our results suggest that although neural crest cells are able to migrate and differentiate in talpid3 gut, their patterning within the gut is dramatically perturbed. In addition, overall gut length is significantly reduced and SMA-positive cells either fail to differentiate or, if present, fail to be organised into circular muscle layers. Thus, these findings suggest that perturbation of Hh signalling in the talpid3 chicken embryo results in malformation of the gastrointestinal tract, disorganised gut smooth muscle, and disrupted patterning of the ENS.
Original languageEnglish
Title of host publicationMechanisms of Development
Publication statusPublished - Aug 2009

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