The formation of blood-brain barrier and vascular integrity depends on the coordinative development of different cell types in the brain. Previous studies have shown that zebrafish bubblehead (bbh) mutant, which has mutation in the betaPix locus, develops spontaneous intracerebral hemorrhage during early development. However, it remains unclear in which brain cells betaPix may function.

On October 24, 2025, the research group headed by Professor Jing-wei Xiong, affiliated with the School of Basic Medical Sciences, The Second Affiliated Hospital, Institute of Biomedical Innovation of Nanchang University, published a research paper entitled Glial betaPix is essential for blood vessel development in the zebrafish brain in the online edition of the journal eLife (DOI: 10.7554/eLife.106665). The finding sheds new light on the regulatory mechanisms underlying neurovascular development in vertebrate models. The paper revealed that the betaPix protein in glial cells plays a crucial role in brain vessel development and the formation of the blood-brain barrier. Through establishing an efficient conditional gene knockout technology in zebrafish, the study found that betaPix has a decisive influence on brain vessel development and integrity in neural glial cells, providing a new perspective for understanding the molecular mechanisms of brain vessel diseases and abnormal blood-brain barrier.

Here, they established a highly efficient conditional knockout method in zebrafish by using homology-directed repair (HDR)-mediated knockin and knockout technology, and generated betaPix conditional trap (betaPix^ct) allele in zebrafish. They found that betaPix in glia, but neither neurons, endothelial cells, nor pericytes, was critical for glial and vascular development and integrity, thus contributing to the formation of blood-brain barrier. Single-cell transcriptome profiling revealed that microtubule aggregation signaling stathmins and pro-angiogenic transcription factors Zfhx3/4 were downregulated in glial and neuronal progenitors, and further genetic analysis suggested that betaPix acted upstream on the PAK1-Stathmin and Zfhx3/4-Vegfaa signaling to regulate glia migration and vascular integrity. This work not only provides a new molecular mechanism for understanding the integrity of the brain vasculature, but also opens up new directions for the study of human brain vascular diseases such as stroke, cerebral hemorrhage, and neurodegenerative disorders.

Professor Jing-wei Xiong from our Institute of Biomedical Innovation/School of Basic Medical Sciences/The Second Affiliated Hospital, together with Professor Zhu Xiaojun and Professor Ding Wanqiu from the College of Future Technology, Peking University, serve as the co-corresponding authors of this paper. ShihChing Chiu, a PhD student from the College of Future Technology, Peking University (now graduated), is the first author. PhD students Qinchao Zhou and Linlu Bai from College of Future Technology, Peking University (now graduated) contributed to the research work. Additionally, Chenglu Xiao from our Institute of Biomedical Innovation/School of Basic Medical Sciences, offered valuable guidance and collaborative support throughout the study.

The original link to the paper is available at https://doi.org/10.7554/eLife.106665.2.