| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
51-194 |
DRI_Background |
denotes |
Studies implicate an important role for the mixed lineage leukemia (Mll) gene in hematopoiesis, mainly through maintaining Hox gene expression. |
| T2 |
195-301 |
DRI_Background |
denotes |
However, the mechanisms underlying Mll-mediated hematopoiesis during embryogenesis remain largely unclear. |
| T3 |
302-398 |
DRI_Outcome |
denotes |
Here, we investigate the role of mll during zebrafish embryogenesis, particularly hematopoiesis. |
| T4 |
399-619 |
DRI_Background |
denotes |
Mll depletion caused severe defects in hematopoiesis as indicated by a lack of blood flow and mature blood cells as well as a significant reduction in expression of hematopoietic progenitor and mature blood cell markers. |
| T5 |
620-706 |
DRI_Background |
denotes |
Furthermore, mll depletion prevented the differentiation of hematopoietic progenitors. |
| T6 |
707-863 |
DRI_Approach |
denotes |
In addition, we identified the N-terminal mini-peptide of Mll that acted as a dominant negative form to disrupt normal function of mll during embryogenesis. |
| T7 |
864-939 |
DRI_Approach |
denotes |
As expected, mll knockdown altered the expression of a subset of Hox genes. |
| T8 |
940-1117 |
DRI_Approach |
denotes |
However, overexpression of these down-regulated Hox genes only partially rescued the blood deficiency, suggesting that mll may target additional genes to regulate hematopoiesis. |
| T9 |
1207-1376 |
DRI_Outcome |
denotes |
Multiple assays indicate that mll inhibited gadd45αa expression and that overexpression of gadd45αa mRNA led to a phenotype similar to the one seen in the mll morphants. |
| T10 |
1377-1590 |
DRI_Approach |
denotes |
Taken together, these findings demonstrate that zebrafish mll plays essential roles in hematopoiesis and that gadd45αa may serve as a potential downstream target for mediating the function of mll in hematopoiesis. |
