A Hox complex activates and potentiates the Epidermal Growth Factor signaling pathway to specify Drosophila oenocytes

Autor: Guolun Wang, Brian Gebelein, David Li-Kroeger, Lisa M. Gutzwiller
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Cancer Research
Embryology
Transcription factor complex
Gene Expression
Biochemistry
Database and Informatics Methods
Epidermal growth factor
Animal Cells
Drosophila Proteins
Hox gene
Genetics (clinical)
ETS transcription factor family
Drosophila Melanogaster
Gene Expression Regulation
Developmental
Sense Organs
Cell Differentiation
Animal Models
Cell biology
Insects
Enhancer Elements
Genetic
Experimental Organism Systems
Drosophila
Signal transduction
Cellular Types
Sequence Analysis
Research Article
Signal Transduction
animal structures
lcsh:QH426-470
Arthropoda
Precursor Cells
Bioinformatics
Nerve Tissue Proteins
Cell fate determination
Biology
Research and Analysis Methods
03 medical and health sciences
Model Organisms
Protein Domains
Sequence Motif Analysis
Proto-Oncogene Proteins
DNA-binding proteins
Genetics
Homeobox
Animals
Gene Regulation
Enhancer
Molecular Biology
Transcription factor
Ecology
Evolution
Behavior and Systematics
Epidermal Growth Factor
Embryos
Organisms
Biology and Life Sciences
Proteins
Cell Biology
Molecular biology
Invertebrates
Regulatory Proteins
lcsh:Genetics
030104 developmental biology
Hepatocytes
Developmental Biology
Transcription Factors
Zdroj: PLoS Genetics
PLoS Genetics, Vol 13, Iss 7, p e1006910 (2017)
ISSN: 1553-7404
1553-7390
Popis: Hox transcription factors specify distinct cell types along the anterior-posterior axis of metazoans by regulating target genes that modulate signaling pathways. A well-established example is the induction of Epidermal Growth Factor (EGF) signaling by an Abdominal-A (Abd-A) Hox complex during the specification of Drosophila hepatocyte-like cells (oenocytes). Previous studies revealed that Abd-A is non-cell autonomously required to promote oenocyte fate by directly activating a gene (rhomboid) that triggers EGF secretion from sensory organ precursor (SOP) cells. Neighboring cells that receive the EGF signal initiate a largely unknown pathway to promote oenocyte fate. Here, we show that Abd-A also plays a cell autonomous role in inducing oenocyte fate by activating the expression of the Pointed-P1 (PntP1) ETS transcription factor downstream of EGF signaling. Genetic studies demonstrate that both PntP1 and PntP2 are required for oenocyte specification. Moreover, we found that PntP1 contains a conserved enhancer (PntP1OE) that is activated in oenocyte precursor cells by EGF signaling via direct regulation by the Pnt transcription factors as well as a transcription factor complex consisting of Abd-A, Extradenticle, and Homothorax. Our findings demonstrate that the same Abd-A Hox complex required for sending the EGF signal from SOP cells, enhances the competency of receiving cells to select oenocyte cell fate by up-regulating PntP1. Since PntP1 is a downstream effector of EGF signaling, these findings provide insight into how a Hox factor can both trigger and potentiate the EGF signal to promote an essential cell fate along the body plan.
Author summary Hox genes encode a conserved family of transcription factors that regulate unique cell types within the distinct morphological structures that arise along the body plan of animals. Hox transcription factors specify different cell fates by regulating the expression of downstream genes, many of which are part of cell signaling pathways. For example, a Hox factor that is only expressed in the Drosophila abdomen (Abdominal-A) activates the release of a signaling molecule (Epidermal Growth Factor, EGF) from a specific neural precursor cell. The cells that receive the signal are induced to become essential hepatocyte-like cells required for metabolism and animal growth. Here, we show that this same Hox factor is not only required for sending the EGF signal, but it also enhances the strength of the signal within the developing hepatocyte-like cells. Importantly, the thoracic Hox factor fails to both induce and enhance the signal, thereby providing a better understanding of how these abdomen-specific cells are generated and distinct morphological structures become regionalized to specific segments of the embryo.
Databáze: OpenAIRE
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