PhD Scientific Days 2025

Poster Session III. - C: Molecular Medicine

The overlooked route: the role of lumbosacral derived neural crest stem cells in extrinsic innervation of the colorectum

Name of the presenter

Gáspár-Halasy Viktória

Institute/workplace of the presenter

Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University

Authors

Viktória Gáspár-Halasy¹, Zsanna Gecse¹, Ádám Soós¹, Csenge Jurenka¹, Emőke Szőcs¹, Bettina Kaczur¹, Nándor Nagy¹

1: Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University

Text of the abstract

The enteric nervous system (ENS), often referred to as the "second brain," comprises approximately 100 million neurons and closely parallels the central nervous system in complexity. It governs essential gastrointestinal functions such as peristalsis, secretion, mucosal transport, immune defense, and endocrine regulation. Developmental abnormalities of the ENS constitute a major etiology of intestinal dysmotility, with Hirschsprung disease (HSCR) representing a well-characterized congenital disorder (~1:5000 live births), defined by variable-length aganglionosis of the distal colon. The pathogenesis of HSCR is primarily attributed to defects in the migration, proliferation, or differentiation of neural crest-derived progenitors that give rise to the ENS. However, hypertrophic extrinsic nerve fibers in the aganglionic segment also contribute to disease pathology, yet their embryological background remains poorly understood.
These extrinsic fibers of the colorectum arise from pelvic ganglia, which originate from the lumbosacral neural crest. In avian model system, this network is further completed with the nerve of Remak—a ganglionated structure peculiar to birds, that serves as a suitable experimental model for studying extrinsic enteric innervation. Lumbosacral neural crest-derived cells also migrate along extrinsic fibers into the submucosa and lamina propria, and notably, such cells have been identified even in HSCR. To study the contribution of lumbosacral neural crest-derived cells during ENS ontogeny, we aim to trace their differentiation dynamics during large intestinal colonization. We also generate neurospheres from avian ENS, providing a novel model system to investigate their regenerative potential. While it remains hypothetical whether these cells can restore enteric ganglia in aganglionic gut, this approach offers a promising experimental system to explore stem cell–based ENS reconstruction.
Grants: NKFI138664; EKÖP-2024-2.1.1-EKÖP-2024-00004