Trithorax maintains the functional heterogeneity of neural stem cells through the transcription factor Buttonhead
- University of Michigan Medical School, United States
Figures
Figure 1 with 1 supplement
trx mutant type II neuroblasts display characteristics of a type I neuroblast.
Key for all figures: all clones are outlined in yellow. Wild-type type II neuroblasts or mutant type I neuroblasts (Dpn+Ase−Pros−; white arrow); Ase− immature INPs (Dpn−Ase−Pros−; white arrowhead); …
Figure 1—figure supplement 1
A diagram of two distinct neuroblast lineages.
A summary of the cell fate marker expression profile in type I and type II neuroblast lineage in the larval brain. NB: neuroblast; GMC: ganglion mother cell; INP: intermediate neural progenitor; imm …
Figure 2
trx mutant type II neuroblast directly generates GMCs.
(A–E) trx is required for the expansion of supernumerary type II neuroblasts in the brat or erm mutant. (A–D) Removing trx function suppresses the expansion of supernumerary type II neuroblasts and …
Figure 3 with 2 supplements
Trx and the core components of the SET/MLL complex maintain a type II neurobalst functional identity dependently on their catalytic activity for H3K4 methylaiton.
(A–B) The function of trx for the H3K4 methylation is required for the maintenance of a type II neuroblast functional identity. (A–B) In the 72-hr clones, a trxZ11 mutant type II neuroblast displays …
Figure 3—figure supplement 1
Decreasing the function of the core components of the SET1/MLL complex leads to a reduction in type II neuroblasts.
(A–E) Knocking down the function of trx, rbbp5, wds or ash2 specifically reduces the number of type II neuroblasts per brain lobe. Scale bar, 20 μm. (F–G) The average number of type II neuroblasts …
Figure 3—figure supplement 2
Generation of the rbbp5null allele and the UAS-rbbp5SG transgene.
(A) The genomic organization of the rbbp5 locus. The rbbp5null allele was generated via imprecise excision of the P(EP)G4226 element, which removes the entire rbbp5 coding region. Yellow squares …
Figure 4 with 2 supplements
Btd likely acts downstream of Trx to maintain a type II neuroblast functional identity.
(A–D) The btd gene is an excellent candidate target of Trx in the type II neuroblast. (A) The btd mRNA is highly enriched in the lysate extracted from larval brain enriched with type II neuroblasts. …
Figure 4—figure supplement 1
Global H3K4 mono- or tri-methylation is not required for maintenance of a type II neuroblast functional identity.
(A–H) The core component of the SET1/MLL complex is required for the global methylation of H3K4. (A, C, E, G) Knocking down the function of ash2 or trr leads to global loss of the H3K4 …
Figure 4—figure supplement 2
Pnt likely functions to specify an INP identity.
(A) Trx directly binds to transcription start site (TSS) of the pntP1 transcript. Quantification of chromatin immunoprecipitated by the indicated antibodies relative to 5% of input. The …
Figure 5
Over-expression of btd is sufficient to instruct a type II neuroblast functional identity in the type I neuroblast.
(A–E) Over-expression of btd is sufficient to elicit a type II neuroblast functional identity. (A–D) In the 72-hr clones, 18% of type I neuroblasts over-expressing btd lose Ase expression and are …
Figure 6
Over-expression of btd restores a type II neuroblast functional identity in trx mutant type II neuroblasts.
(A–D) Overexpression of btd reinstates the ability to generate INPs in trx mutant type II neuroblasts. (A–B) In the 72-hr clones, while the control trx mutant type II neuroblasts are surrounded by …
Figure 7
A summary model.
The Trx histone methyltransferase complex maintains the type II neuroblast functional identity through the btd gene whereas it promotes INP identity specification through the pnt gene.
Tables
Table 1
Summary of the marker expression profile in various genetic backgrounds
| Genotype | Neuroblast type | Dpn | Ase | Pros* | PntP1 |
|---|---|---|---|---|---|
| wild-type | I | + | + | + | − |
| wild-type | II | + | − | − | + |
| Trx−/− | I | + | + | + | − |
| Trx−/− | II | + | + | + | − |
| Rbbp5−/− | I | + | + | + | − |
| Rbbp5−/− | II | + | + | + | − |
| btd−/− | I | + | + | + | − |
| btd−/− | II | + | − | − | + |
-
‘+’ indicates detected marker expression whereas ‘−’ indicates lack of marker expression. ‘*’ indicates basal asymmetric localization at the basal cortex in mitotic neuroblasts.
