Article

Genome-Wide Analysis Reveals a Major Role in Cell Fate Maintenance and an Unexpected Role in Endoreduplication for the Drosophila FoxA Gene Fork Head

Stockholm University, Sweden
PLoS ONE (Impact Factor: 3.53). 06/2011; 6(6):e20901. DOI: 10.1371/journal.pone.0020901
Source: PubMed

ABSTRACT Transcription factors drive organogenesis, from the initiation of cell fate decisions to the maintenance and implementation of these decisions. The Drosophila embryonic salivary gland provides an excellent platform for unraveling the underlying transcriptional networks of organ development because Drosophila is relatively unencumbered by significant genetic redundancy. The highly conserved FoxA family transcription factors are essential for various aspects of organogenesis in all animals that have been studied. Here, we explore the role of the single Drosophila FoxA protein Fork head (Fkh) in salivary gland organogenesis using two genome-wide strategies. A large-scale in situ hybridization analysis reveals a major role for Fkh in maintaining the salivary gland fate decision and controlling salivary gland physiological activity, in addition to its previously known roles in morphogenesis and survival. The majority of salivary gland genes (59%) are affected by fkh loss, mainly at later stages of salivary gland development. We show that global expression of Fkh cannot drive ectopic salivary gland formation. Thus, unlike the worm FoxA protein PHA-4, Fkh does not function to specify cell fate. In addition, Fkh only indirectly regulates many salivary gland genes, which is also distinct from the role of PHA-4 in organogenesis. Our microarray analyses reveal unexpected roles for Fkh in blocking terminal differentiation and in endoreduplication in the salivary gland and in other Fkh-expressing embryonic tissues. Overall, this study demonstrates an important role for Fkh in determining how an organ preserves its identity throughout development and provides an alternative paradigm for how FoxA proteins function in organogenesis.

Download full-text

Full-text

Available from: Rika Maruyama, Jun 27, 2015
1 Follower
 · 
110 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Epithelial tubular organs are essential for life in higher organisms and include the pancreas and other secretory organs that function as biological factories for the synthesis and delivery of secreted enzymes, hormones, and nutrients essential for tissue homeostasis and viability. The lungs, which are necessary for gas exchange, vocalization, and maintaining blood pH, are organized as highly branched tubular epithelia. Tubular organs include arteries, veins, and lymphatics, high-speed passageways for delivery and uptake of nutrients, liquids, gases, and immune cells. The kidneys and components of the reproductive system are also epithelial tubes. Both the heart and central nervous system of many vertebrates begin as epithelial tubes. Thus, it is not surprising that defects in tube formation and maintenance underlie many human diseases. Accordingly, a thorough understanding how tubes form and are maintained is essential to developing better diagnostics and therapeutics. Among the best-characterized tubular organs are the Drosophila salivary gland and trachea, organs whose relative simplicity have allowed for in depth analysis of gene function, yielding key mechanistic insight into tube initiation, remodeling and maintenance. Here, we review our current understanding of salivary gland and trachea formation - highlighting recent discoveries into how these organs attain their final form and function.
    Developmental Dynamics 01/2012; 241(1):119-35. DOI:10.1002/dvdy.22775 · 2.67 Impact Factor
  • Source
    Embryogenesis, 04/2012; , ISBN: 978-953-51-0466-7
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hox genes are a group of genes that specify structures along the anteroposterior axis in bilaterians. Although in many cases they do so by modifying a homologous structure with a different (or no) Hox input, there are also examples of Hox genes constructing new organs with no homology in other regions of the body. Hox genes determine structures though the regulation of targets implementing cellular functions and by coordinating cell behavior. The genetic organization to construct or modify a certain organ involves both a genetic cascade through intermediate transcription factors and a direct regulation of targets carrying out cellular functions. In this review I discuss new data from genome-wide techniques, as well as previous genetic and developmental information, to describe some examples of Hox regulation of different cell functions. I also discuss the organization of genetic cascades leading to the development of new organs, mainly using Drosophila melanogaster as the model to analyze Hox function.
    01/2013; 2013:738257. DOI:10.1155/2013/738257