Justus-Liebig-Universitaet Giessen, Institut für Allgemeine und Spezielle Zoologie, Allgemeine Zoologie und Entwicklungsbiologie, Stephanstraße 24, 35390 Gießen, Germany.
The Sahlgrenska Academy at the University of Gothenburg, Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, Medicinaregatan 9A, 41390 Gothenburg, Sweden.
Development. 2019 Jan 16;146(2):dev168948. doi: 10.1242/dev.168948.
Basement membranes (BMs) are specialized layers of extracellular matrix (ECM) mainly composed of Laminin, type IV Collagen, Perlecan and Nidogen/entactin (NDG). Recent studies challenged the initially proposed role of NDG as a major ECM linker molecule by revealing dispensability for viability and BM formation. Here, we report the characterization of the single gene in Embryonic expression was primarily observed in mesodermal tissues and the chordotonal organs, whereas NDG protein localized to all BMs. Although loss of Laminin strongly affected BM localization of NDG, -null mutants exhibited no overt changes in the distribution of BM components. Although mutants were viable, loss of NDG led to ultrastructural BM defects that compromised barrier function and stability Moreover, loss of NDG impaired larval crawling behavior and reduced responses to vibrational stimuli. Further morphological analysis revealed accompanying defects in the larval peripheral nervous system, especially in the chordotonal organs and the neuromuscular junction (NMJ). Taken together, our analysis suggests that NDG is not essential for BM assembly but mediates BM stability and ECM-dependent neural plasticity during development.
基底层（BMs）是细胞外基质（ECM）的特殊层，主要由层粘连蛋白、IV 型胶原、Perlecan 和 Nidogen/entactin（NDG）组成。最近的研究挑战了最初提出的 NDG 作为主要 ECM 连接分子的作用，揭示了其在生存能力和 BM 形成方面的非必需性。在这里，我们报告了单个基因在胚胎发育中的特征，其表达主要在中胚层组织和听弦器官中观察到，而 NDG 蛋白定位于所有的 BMs。尽管层粘连蛋白的缺失强烈影响了 NDG 在 BM 上的定位，但-ND 突变体在 BM 成分的分布上没有明显变化。虽然突变体是有活力的，但 NDG 的缺失导致了 BM 的超微结构缺陷，损害了屏障功能和稳定性。此外，NDG 的缺失损害了幼虫的爬行行为，并降低了对振动刺激的反应。进一步的形态学分析显示，幼虫周围神经系统也伴随着缺陷，特别是在听弦器官和神经肌肉连接处（NMJ）。综上所述，我们的分析表明，NDG 对于 BM 的组装不是必需的，但在幼虫发育过程中，它介导了 BM 的稳定性和 ECM 依赖性的神经可塑性。
