@article {1458, title = {The Hox gene uses Doublesex as a cofactor to promote neuroblast apoptosis in the central nervous system [Transgenic Fly Facility]}, journal = {Development}, volume = {146}, year = {2019}, month = {2019 08 22}, abstract = {

Highly conserved DM domain-containing transcription factors (Doublesex/MAB-3/DMRT1) are responsible for generating sexually dimorphic features. In the central nervous system, a set of Doublesex (Dsx)-expressing neuroblasts undergo apoptosis in females whereas their male counterparts proliferate and give rise to serotonergic neurons crucial for adult mating behaviour. Our study demonstrates that the female-specific isoform of Dsx collaborates with Hox gene () to bring about this apoptosis. Biochemical results suggest that proteins AbdB and Dsx interact through their highly conserved homeodomain and DM domain, respectively. This interaction is translated into a cooperative binding of the two proteins on the apoptotic enhancer in the case of females but not in the case of males, resulting in female-specific activation of apoptotic genes. The capacity of AbdB to use the sex-specific isoform of Dsx as a cofactor underlines the possibility that these two classes of protein are capable of cooperating in selection and regulation of target genes in a tissue- and sex-specific manner. We propose that this interaction could be a common theme in generating sexual dimorphism in different tissues across different species.

}, keywords = {Animals, Apoptosis, DNA-Binding Proteins, Drosophila, Drosophila Proteins, Female, Gene Expression Regulation, Developmental, Genes, Homeobox, Homeodomain Proteins, Male, Neural Stem Cells, Protein Isoforms, Sex Characteristics}, issn = {1477-9129}, doi = {10.1242/dev.175158}, author = {Ghosh, Neha and Bakshi, Asif and Khandelwal, Risha and Rajan, Sriivatsan Govinda and Joshi, Rohit} } @article {683, title = {Combinatorial action of Grainyhead, Extradenticle and Notch in regulating Hox mediated apoptosis in Drosophila larval CNS.}, journal = {PLoS Genet}, volume = {13}, year = {2017}, month = {2017 Oct}, pages = {e1007043}, abstract = {

Hox mediated neuroblast apoptosis is a prevalent way to pattern larval central nervous system (CNS) by different Hox genes, but the mechanism of this apoptosis is not understood. Our studies with Abdominal-A (Abd-A) mediated larval neuroblast (pNB) apoptosis suggests that AbdA, its cofactor Extradenticle (Exd), a helix-loop-helix transcription factor Grainyhead (Grh), and Notch signaling transcriptionally contribute to expression of RHG family of apoptotic genes. We find that Grh, AbdA, and Exd function together at multiple motifs on the apoptotic enhancer. In vivo mutagenesis of these motifs suggest that they are important for the maintenance of the activity of the enhancer rather than its initiation. We also find that Exd function is independent of its known partner homothorax in this apoptosis. We extend some of our findings to Deformed expressing region of sub-esophageal ganglia where pNBs undergo a similar Hox dependent apoptosis. We propose a mechanism where common players like Exd-Grh-Notch work with different Hox genes through region specific enhancers to pattern respective segments of larval central nervous system.

}, keywords = {Amino Acid Sequence, Animals, Apoptosis, Central Nervous System, DNA-Binding Proteins, Drosophila, Drosophila Proteins, Enhancer Elements, Genetic, Female, Gene Expression Regulation, Developmental, Genes, Homeobox, Homeodomain Proteins, Larva, Male, Nuclear Proteins, Receptors, Notch, Transcription Factors}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1007043}, author = {Khandelwal, Risha and Sipani, Rashmi and Govinda Rajan, Sriivatsan and Kumar, Raviranjan and Joshi, Rohit} }