Brain expansion promoted by polycomb-mediated anterior enhancement of a neural stem cell proliferation program

Abstract

During central nervous system (CNS) development, genetic programs establish neural stem cells and drive both stem and daughter cell proliferation. However, the prominent anterior expansion of the CNS implies anterior–posterior (A–P) modulation of these programs. In Drosophila , a set of neural stem cell factors acts along the entire A–P axis to establish neural stem cells. Brain expansion results from enhanced stem and daughter cell proliferation, promoted by a Polycomb Group (PcG)->Homeobox (Hox) homeotic network. But how does PcG->Hox modulate neural-stem-cell–factor activity along the A–P axis? We find that the PcG->Hox network creates an A–P expression gradient of neural stem cell factors, thereby driving a gradient of proliferation. PcG mutants can be rescued by misexpression of the neural stem cell factors or by mutation of one single Hox gene. Hence, brain expansion results from anterior enhancement of core neural-stem-cell–factor expression, mediated by PcG repression of brain Hox expression.

Sequential activation of Notch and Grainyhead gives apoptotic competence to Abdominal-B expressing larval neuroblasts in Drosophila Central nervous system

“…and A10 [4,14,34,35]. Subsequently these NBs enter quiescence and start dividing again in early larval stages ( Fig 1A).…”

“…This is mainly contributed by a gradient of NB proliferation as well as a switch in cell division mode (from Type I>0) along the AP axis (regulated by Hox genes). These molecular events together reduce the number of cells in these segments and lay the foundation of a wedge shaped CNS tapering towards the terminal region later in development [34,35].…”

“…First, Abd-B prevents formation of certain lineages altogether in terminal segments of embryonic CNS by collaborating with TF Caudal [52]. Second, Abd-B reduces the proliferation of NBs in terminal segments compared to NBs in thoracic and abdominal segments [34,35]. Third, Abd-B gives a more derived character to the NBs in the terminal region [52].…”

“…Third, Abd-B gives a more derived character to the NBs in the terminal region [52]. This results in a precocious switch in cell division mode (from Type I>0) for the terminal NBs as compared to abdominal and thoracic NBs [34,35], thereby resulting in smaller lineages. These events are followed by Abd-B mediated apoptosis of majority of the NBs in terminal segments of embryonic CNS [4,34], further limiting the number of cells in this region.…”

DrosophilaNeuroblast Selection Gated by Notch, Snail, SoxB and EMT Gene Interplay

“…As anticipated from previous studies, we observed a reduction in NB numbers in both SoxN and wor mutants ( Figure 3A-C, 3F). The UAS-Quad and -Quad D combinatorial expression, which includes SoxN or wor, can trigger massive ectopic NB generation in the embryonic ectoderm or wing imaginal discs ( Figure 1E-G) (Bahrampour et al, 2017;Bahrampour et al, 2019). However, we did not previously test the effects of single SoxN or wor misexpression from an early Gal4 driver.…”