Abstract The Dlx genes play an important role in the differentiation and migration of gamma-aminobutyric acid (GABA) interneurons of mice. GABAergic interneurons are born in the proliferative zones of the ventral telencephalon and migrate to the cortex early during mouse development. Single Dlx mutant mice show only subtle phenotypes. However, the migration of immature interneurons is blocked in the ventral telencephalon of Dlx1/Dlx2 double mutant mice leading to reduction of GABAergic interneurons in the cortex. Also, Dlx5/Dlx6 expression is almost entirely absent in the forebrain, most probably due to cross-regulatory mechanisms. In zebrafish, the role of dlx genes in GABAergic interneuron development is unknown. By injecting Morpholino, we double knocked down dlx1 and dlx2 genes in wildtype zebrafish to investigate the function of the two genes in zebrafish GABAergic interneuron development. By comparing different subsets of GABAergic interneuron development in wildtype and dlx1/2 morphant zebrafish forebrain, we found out that at 3dpf, 4dpf and 7dpf, double knockdown of dlx1 and dlx2 genes in zebrafish remarkably reduced the number of Calbindin-, Somatostatin- and Parvalbumin-positive GABAergic neurons, whereas the development of Calretinin-positive neurons is slightly affected. These results suggest that in zebrafish, dlx1a and dlx2a genes are important for the development of certain subtypes of GABAergic interneurons (Calbindin-, Somatostatin- and Parvalbumin-positive neurons) and may have minor influence on Calretinin-positive neuron development. This also suggests that different regulatory mechanisms are involved in the development of the different subtypes of GABAergic interneurons.

Abstract The Dlx genes play an important role in the differentiation and migration of gamma-aminobutyric acid (GABA) interneurons of mice. GABAergic interneurons are born in the proliferative zones of the ventral telencephalon and migrate to the cortex early during mouse development. Single Dlx mutant mice show only subtle phenotypes. However, the migration of immature interneurons is blocked in the ventral telencephalon of Dlx1/Dlx2 double mutant mice leading to reduction of GABAergic interneurons in the cortex. Also, Dlx5/Dlx6 expression is almost entirely absent in the forebrain, most probably due to cross-regulatory mechanisms. In zebrafish, the role of dlx genes in GABAergic interneuron development is unknown. By injecting Morpholino, we double knocked down dlx1 and dlx2 genes in wildtype zebrafish to investigate the function of the two genes in zebrafish GABAergic interneuron development. By comparing different subsets of GABAergic interneuron development in wildtype and dlx1/2 morphant zebrafish forebrain, we found out that at 3dpf, 4dpf and 7dpf, double knockdown of dlx1 and dlx2 genes in zebrafish remarkably reduced the number of Calbindin-, Somatostatin- and Parvalbumin-positive GABAergic neurons, whereas the development of Calretinin-positive neurons is slightly affected. These results suggest that in zebrafish, dlx1a and dlx2a genes are important for the development of certain subtypes of GABAergic interneurons (Calbindin-, Somatostatin- and Parvalbumin-positive neurons) and may have minor influence on Calretinin-positive neuron development. This also suggests that different regulatory mechanisms are involved in the development of the different subtypes of GABAergic interneurons.

Abstract The Dlx genes play an important role in the differentiation and migration of gamma-aminobutyric acid (GABA) interneurons of mice. GABAergic interneurons are born in the proliferative zones of the ventral telencephalon and migrate to the cortex early during mouse development. Single Dlx mutant mice show only subtle phenotypes. However, the migration of immature interneurons is blocked in the ventral telencephalon of Dlx1/Dlx2 double mutant mice leading to reduction of GABAergic interneurons in the cortex. Also, Dlx5/Dlx6 expression is almost entirely absent in the forebrain, most probably due to cross-regulatory mechanisms. In zebrafish, the role of dlx genes in GABAergic interneuron development is unknown. By injecting Morpholino, we double knocked down dlx1 and dlx2 genes in wildtype zebrafish to investigate the function of the two genes in zebrafish GABAergic interneuron development. By comparing different subsets of GABAergic interneuron development in wildtype and dlx1/2 morphant zebrafish forebrain, we found out that at 3dpf, 4dpf and 7dpf, double knockdown of dlx1 and dlx2 genes in zebrafish remarkably reduced the number of Calbindin-, Somatostatin- and Parvalbumin-positive GABAergic neurons, whereas the development of Calretinin-positive neurons is slightly affected. These results suggest that in zebrafish, dlx1a and dlx2a genes are important for the development of certain subtypes of GABAergic interneurons (Calbindin-, Somatostatin- and Parvalbumin-positive neurons) and may have minor influence on Calretinin-positive neuron development. This also suggests that different regulatory mechanisms are involved in the development of the different subtypes of GABAergic interneurons.

Abstract The Dlx genes play an important role in the differentiation and migration of gamma-aminobutyric acid (GABA) interneurons of mice. GABAergic interneurons are born in the proliferative zones of the ventral telencephalon and migrate to the cortex early during mouse development. Single Dlx mutant mice show only subtle phenotypes. However, the migration of immature interneurons is blocked in the ventral telencephalon of Dlx1/Dlx2 double mutant mice leading to reduction of GABAergic interneurons in the cortex. Also, Dlx5/Dlx6 expression is almost entirely absent in the forebrain, most probably due to cross-regulatory mechanisms. In zebrafish, the role of dlx genes in GABAergic interneuron development is unknown. By injecting Morpholino, we double knocked down dlx1 and dlx2 genes in wildtype zebrafish to investigate the function of the two genes in zebrafish GABAergic interneuron development. By comparing different subsets of GABAergic interneuron development in wildtype and dlx1/2 morphant zebrafish forebrain, we found out that at 3dpf, 4dpf and 7dpf, double knockdown of dlx1 and dlx2 genes in zebrafish remarkably reduced the number of Calbindin-, Somatostatin- and Parvalbumin-positive GABAergic neurons, whereas the development of Calretinin-positive neurons is slightly affected. These results suggest that in zebrafish, dlx1a and dlx2a genes are important for the development of certain subtypes of GABAergic interneurons (Calbindin-, Somatostatin- and Parvalbumin-positive neurons) and may have minor influence on Calretinin-positive neuron development. This also suggests that different regulatory mechanisms are involved in the development of the different subtypes of GABAergic interneurons.

The heterogeneous nature of acute myeloid leukemia (AML) worsens the results of patients treated with standard therapy. Understanding the processes of leukemogenesis can contribute to identification of more appropriate treatment. Family of DLX genes (Distal-less homeobox), belonging to the homeobox genes, are associated with haematological malignancies and solid tumors. In the analysis of expression data, the low level of the DLX1 gene was associated with a worse prognosis of patients with AML. In this work we studied phenotypic changes of cell lines with different expression of the DLX1 gene. We silenced the DLX1 gene in AML cell line (sh cells) and compared it to the parental line with higher expression of DLX1 (NSC cells). By cell cycle analysis and apoptosis assays in vitro and in vivo, we have observed the arrest of sh cells in the G0 phase and a lower number of apoptotic cells. Differences were found when measuring the absolute number of cells in time. In in vitro conditions there were less sh cells, in in vivo environment there was significantly higher number of sh cells engrafted in comparison to NSC cells. Further results have shown that sh cells have lower levels of pro-apoptotic proteins and exhibit a higher level of TGF-β targeting PAI-1 gene that activates replicative senescence. We...