Abstract
Stem cells that indirectly generate differentiated cells through intermediate progenitors drives vertebrate brain evolution. Due to a lack of lineage information, how stem cell functionality, including the competency to generate intermediate progenitors, becomes extinguished during progenitor commitment remains unclear. Type II neuroblasts in fly larval brains divide asymmetrically to generate a neuroblast and a progeny that commits to an intermediate progenitor (INP) identity. We identified Tailless (Tll) as a master regulator of type II neuroblast functional identity, including the competency to generate INPs. Successive expression of transcriptional repressors functions through Hdac3 to silence tll during INP commitment. Reducing repressor activity allows re-activation of Notch in INPs to ectopically induce tll expression driving supernumerary neuroblast formation. Knocking-down hdac3 function prevents downregulation of tll during INP commitment. We propose that continual inactivation of stem cell identity genes allows intermediate progenitors to stably commit to generating diverse differentiated cells during indirect neurogenesis.
Highlights
Indirect generation of differentiated cell types through intermediate progenitors allows tissue-specific stem cells to scale their progeny output to accommodate the development of appropriately sized organs in proportion to organism sizes
These results demonstrate that transient Insb overexpression can induce supernumerary type II neuroblasts to synchronously transition into intermediate progenitor (INP) in brat-null brains
The mechanisms controlling the functional identity of outer subventricular zone (OSVZ) neural stem cells, including the competency to generate intermediate progenitors, remain unknown
Summary
Indirect generation of differentiated cell types through intermediate progenitors allows tissue-specific stem cells to scale their progeny output to accommodate the development of appropriately sized organs in proportion to organism sizes. The competency to generate intermediate progenitors and the maintenance of an undifferentiated state must be coordinately downregulated in stem cell progeny to ensure generation of differentiated cell types. Polycomb-mediated gene repression is thought to inactivate stem-cell-specific genes during differentiation (Tsuboi et al, 2019). Loss of function of Polycomb Repressive Complex 2 (PRC2) did not lead to intermediate progenitors reverting into neural stem cells (Abdusselamoglu et al, 2019). The mechanisms that extinguish stem cell functionality during progenitor commitment remains poorly understood
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