PhD Scientific Days 2022

Molecular Sciences I. (Poster discussion will take place in the Aula during the Coffee Break)

The role of CXCR4-CXCL12 signaling in extrinsic innervation of the hindgut enteric nervous system development

Text of the abstract

Introduction: The gastrointestinal tract is innervated by the extensive intrinsic network of the enteric nervous system (ENS) and by extrinsic afferent and efferent axons of the peripheral ganglia. The nerve of Remak (NoR) is a sacral neural crest-derived (NCC) structure, an avian-specific ganglionated structure that extends from the cloaca to the proximal midgut and has role in extrinsic innervation of the distal gut. As the caudal pair of NoR, the pelvic plexus contributes with extrinsic fibers to the hindgut innervation, which is also found in mammals. The molecular mechanism of NoR- and pelvic plexus derived axon growth is unknown. In vertebrates the presence of CXCR4, a cell surface receptor for the chemokine stromal cell-derived factor-1 (SDF1; CXCL12) is responsible for several embryonic developmental processes including migration of neural crest cells, neuronal survival and axon pathfinding.
Aims: Our aim is following the precise spatiotemporal expression of CXCR4/CXCL12 molecules during ontogeny of ENS and showing of the function of CXCR4-CXCL12 signaling in extrinsic axon growth of the developing hindgut.
Methods: We have employed the wide repertoire of the embryomanipulation technics: chimeric tissue recombination, microbead implantation, chorioallantoic membrane transplantation, organ cultures; and in situ hybridization, combined with immunofluorescence.
Result and Conclusion: We have observed specific CXCR4 expression on NoR and pelvic plexus derived (in mammalian model as well) nerve fibers. In contrast, CXCL12 expression was localized in the hindgut mesenchyme and enteric ganglia. Embryonic tissue recombinants of hindgut and NoR cultured in presence of excess CXCL12 results in significant increase of NCC migration and axon projection from the NoR, while inhibition of CXCR4 signaling with AMD3100 disrupt their migration out of explant, suggesting a novel role for CXCR4/CXCL12 signaling in the extrinsic innervation of the colorectum.
Funding: Our work is supported by NKFI 138664.

E-mail address: halasy.viktoria@semmelweis-univ.hu
University and Doctoral School: Semmelweis University; Doctoral School of Molecular Medicine; Embryology, Theoretical, Experimental and Clinical Developmental Biology Program
Supervisor: Dr. Nándor Nagy
Preferred form of presentation: oral presentation