Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, Budapest 1094, Hungary.
Department of Pediatric Surgery, Pediatric Surgery Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Development. 2023 Apr 15;150(8). doi: 10.1242/dev.201289. Epub 2023 Apr 20.
The gastrointestinal tract is innervated by an intrinsic neuronal network, known as the enteric nervous system (ENS), and by extrinsic axons arising from peripheral ganglia. The nerve of Remak (NoR) is an avian-specific sacral neural crest-derived ganglionated structure that extends from the cloaca to the proximal midgut and, similar to the pelvic plexus, provides extrinsic innervation to the distal intestine. The molecular mechanisms controlling extrinsic nerve fiber growth into the gut is unknown. In vertebrates, CXCR4, a cell-surface receptor for the CXCL12 chemokine, regulates migration of neural crest cells and axon pathfinding. We have employed chimeric tissue recombinations and organ culture assays to study the role of CXCR4 and CXCL12 molecules in the development of colorectal innervation. CXCR4 is specifically expressed in nerve fibers arising from the NoR and pelvic plexus, while CXCL12 is localized to the hindgut mesenchyme and enteric ganglia. Overexpression of CXCL12 results in significantly enhanced axonal projections to the gut from the NoR, while CXCR4 inhibition disrupts nerve fiber extension, supporting a previously unreported role for CXCR4 and CXCL12 signaling in extrinsic innervation of the colorectum.
胃肠道受固有神经网络（即肠神经系统）和外周神经节起源的外轴突支配。雷马克神经（NoR）是一种鸟类特异性的骶神经嵴来源的神经节结构，从泄殖腔延伸到近端中肠，类似于骨盆丛，为远端肠道提供外源性神经支配。控制外源性神经纤维生长进入肠道的分子机制尚不清楚。在脊椎动物中，CXCR4 是趋化因子 CXCL12 的细胞表面受体，调节神经嵴细胞的迁移和轴突寻路。我们采用嵌合体组织重组和器官培养实验来研究 CXCR4 和 CXCL12 分子在结直肠支配发育中的作用。CXCR4 特异性表达于起源于 NoR 和骨盆丛的神经纤维中，而 CXCL12 定位于后肠间质和肠神经节中。CXCL12 的过表达导致 NoR 向肠道的轴突投射显著增强，而 CXCR4 抑制破坏神经纤维的延伸，支持 CXCR4 和 CXCL12 信号在结直肠外源性神经支配中的先前未报道的作用。
