National Yang Ming Chiao Tung University

04/17/2024 | Press release | Distributed by Public on 04/17/2024 01:23

Research on Brain-Nerve Uncovers Key Lung Development Gene: Offering Insights into Tumor Formation and New Treatment Approaches

Translated by Hsuchuan
Edited by Chance Lai

A groundbreaking study has shed light on the pivotal role of a gene known as Nolz1 in both brain and lung development, with its absence potentially leading to lung abnormalities. This discovery holds promise for a deeper understanding of the pathogenesis of lung developmental defects, paving the way for potential therapeutic interventions. This research was published in Development under the title "The Fgf9-Nolz1-Wnt2 axis regulates morphogenesis of the lung".

Analyzing the Critical Role of the 'Nolz1' Gene in Lung Development
After the removal of the Nolz-1 gene, the morphology of the five pulmonary lobes in mice (shown in the right panel) exhibits significant atrophy.

Led by Professor Fu-Chin Liu and Dr. Shih-Yun Chen from the Institute of Neuroscience (INS) at National Yang Ming Chiao Tung University (NYCU), the research team has experimentally confirmed the crucial role of the Nolz1 gene in the early development of lung cells. Defects in the Nolz1 gene are found to result in reduced proliferation of lung interstitial cells, abnormal differentiation of epithelial cells, and even diminished branching of bronchi, significantly impacting lung function.

Furthermore, the team has identified the upstream and downstream genes influencing Nolz1, revealing that lung morphogenesis is regulated through the "Fgf9-Nolz1-Wnt2" signaling pathway. This novel genetic signaling pathway was observed experimentally in mice with deleted Nolz1 genes, where administering recombinant Wnt2 protein effectively mitigated the lung developmental defects caused by gene deletion. Additionally, administering recombinant Fgf9 protein increased Nolz1 expression in the lungs of normal mice, indicating Fgf9 as an upstream gene of Nolz1.

Professor Liu emphasized that this new genetic signaling pathway not only constitutes a crucial regulatory mechanism in normal lung development but also aids scientists in understanding the pathological basis of Nolz1 gene mutations, such as in the formation of lung cancer. Overall, this discovery significantly advances our understanding of lung morphogenesis.

The Multi-Faceted Influence of Nolz1 Gene

Nolz1 has been identified as a crucial gene in the evolution of various animal species. Previous studies have shown that homologous genes of Nolz1 affect the development of fruit fly tracheae and that the absence of Nolz1 leads to abnormal development of brain neural cells. However, this study reveals a cross-disciplinary impact of the same gene from neurology to pulmonology, indicating its influence on brain neural cells and lung development.

Professor Liu noted that the research team initially focused on the neurodevelopment of mammals, given the high expression of Nolz1 in both the brain and lungs during early development. However, the birth of mice with Nolz1 gene deletions resulted in incomplete lung development and subsequent death, prompting the investigation of Nolz1 gene functions in lung development and speculating on its potential impact on mammalian lung development.

In conclusion, this research finding represents a significant breakthrough in understanding organ development. The pivotal role of the Nolz1 gene has been validated not only in neurodevelopment but also in lung development, underscoring its critical significance. This discovery holds profound implications for understanding the formation of lung cancer and offers novel insights for developing more effective therapeutic strategies in the future.

Summary diagram of the research.