This research identifies a specialized genetic mechanism that drives microglia development during the earliest stages of life. While most immune cells depend on a specific Zeb2 enhancer for their formation, scientists discovered that microglia and other macrophages from primitive hematopoiesis bypass this requirement. Instead, the transcription factors Maf and Jun activate the Zeb2 gene through a unique pathway found only in early yolk sac progenitors. Experimental results show that removing Maf severely disrupts the creation of these essential brain immune cells. Conversely, introducing both Maf and Jun into adult bone marrow can force the activation of this early developmental program. These findings reveal why microglia possess a distinct cellular identity compared to other tissue-resident macrophages.

References:

• Chen J, Du S, Cheng W, et al. Transcription factor Maf promotes expression of repressor Zeb2 to drive microglia development in primitive hematopoiesis[J]. Immunity, 2026, 59(1): 48-59. e5.