Genes are crucial for organ growth and development. While studying cranial nerves, scientists have found that a particular gene known as Nolz1 in the brain affects the development of cranial nerves. Deletion of this gene could result in lung abnormalities. This finding facilitates a better understating of pathology in pulmonary development and may lead to potential treatments in the future.
Led by Professor Fu-Chin Liu and Dr. Shih-Yun Chen at the Institute of Neuroscience (INS) of National Yang Ming Chiao Tung University (NYCU), the research team has experimentally proven that Nolz1 genes play an important role in the early cellular development process, leading to the formation of the lungs by animal models. The depletion of Nolz1 genes can cause defects such as reduced proliferation of interstitial cells in the lungs, abnormal epithelial cell differentiation, and even a decrease in bronchial branches. Those defects will seriously affect pulmonary functions.
Besides, the research team also found the upstream and downstream genes affecting Nolz1, demonstrating that pulmonary morphological development has been modulating via “Fgf9-Nolz1-Wnt2,” a newly found gene signaling pathway. This new gene signaling pathway was established by observing mouse lungs in the experiment with the Nolz1 gene knocked out, which showed a reduction in pulmonary development defects after providing the Wnt2 recombinant protein. Besides, after providing the Fgf9 recombinant protein, the Nolz1 expression in the normal mouse lungs was increased, suggesting that Fgf9 is the upstream gene of Nolz1. Fu-Chin Liu indicates that this new gene signaling pathway is the key modulating mechanism for normal pulmonary development and facilitates scientists to understand the pathology foundation related to Nolz1gene mutation, such as the development of lung cancer. This finding represents an outstanding achievement in understanding pulmonary morphological development.
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. In addition, the birth of mice with Nolz1 gene deletions could not survive due to incomplete pulmonary development, prompting the investigation of Nolz1 gene functions in lung development and speculating on its potential impact on mammalian lung development.
This finding was published in the scientific journal Development, facilitating an understanding of Nolz1 genes-related pathology during the development of pulmonary tumors, which paves another new possible way for research and treatment in pulmonary-related disease.