Combinatorial action of Grainyhead, Extradenticle and Notch in regulating Hox mediated apoptosis in Drosophila larval CNS

Autor: Risha Khandelwal, Sriivatsan G. Rajan, Raviranjan Kumar, Rohit Joshi, Rashmi Sipani
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Central Nervous System
Male
Cancer Research
Apoptosis
Nervous System
Biochemistry
Database and Informatics Methods
Binding Analysis
0302 clinical medicine
RNA interference
Cell Signaling
Medicine and Health Sciences
Drosophila Proteins
Hox gene
Genetics (clinical)
Genetics
Regulation of gene expression
Notch Signaling
Cell Death
Receptors
Notch

Genes
Homeobox

Gene Expression Regulation
Developmental

Nuclear Proteins
Nucleic acids
Enhancer Elements
Genetic

Genetic interference
Cell Processes
Larva
Epigenetics
Drosophila
Female
Anatomy
Sequence Analysis
Research Article
Signal Transduction
animal structures
lcsh:QH426-470
Bioinformatics
Notch signaling pathway
Biology
Research and Analysis Methods
03 medical and health sciences
Neuroblast
Sequence Motif Analysis
DNA-binding proteins
Animals
Amino Acid Sequence
Enhancer
Molecular Biology Techniques
Transcription factor
Molecular Biology
Ecology
Evolution
Behavior and Systematics

Chemical Characterization
Homeodomain Proteins
fungi
Biology and Life Sciences
Proteins
Cell Biology
lcsh:Genetics
030104 developmental biology
Homeobox
RNA
Gene expression
030217 neurology & neurosurgery
Cloning
Transcription Factors
Zdroj: PLoS Genetics
PLoS Genetics, Vol 13, Iss 10, p e1007043 (2017)
ISSN: 1553-7404
1553-7390
Popis: 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.
Author summary Specification of the head to tail axis of the developing central nervous system is carried out by Hox genes. Hox mediated programmed cell death of the neural progenitor cells plays an important role in specification of this axis, but the molecular mechanism of this phenomenon is not well understood. We have studied this phenomenon in abdominal and subesophageal regions of larval central nervous system of Drosophila. We find that different Hox genes use a combination of common players (Extradenticle, Grainyhead and Notch) but employ region specific enhancers to cause progenitor cell death in different segments of developing central nervous system.
Databáze: OpenAIRE