abdominal Aspecifies one cell type inDrosophilaby regulating one principal target gene

Abstract

The Hox/homeotic genes encode transcription factors that generate segmental diversity during Drosophila development. At the level of the whole animal, they are believed to carry out this role by regulating a large number of downstream genes. Here we address the unresolved issue of how many Hox target genes are sufficient to define the identity of a single cell. We focus on the larval oenocyte, which is restricted to the abdomen and induced in response to a non-cell autonomous, transient and highly selective input from abdominal A (abdA). We use Hox mutant rescue assays to demonstrate that this function of abdA can be reconstituted by providing Rhomboid (Rho), a processing factor for the EGF receptor ligand, secreted Spitz. Thus, in order to make an oenocyte, abdA regulates just one principal target, rho, that acts at the top of a complex hierarchy of cell-differentiation genes. These studies strongly suggest that, in at least some contexts, Hox genes directly control only a few functional targets within each nucleus. This raises the possibility that much of the overall Hox downstream complexity results from cascades of indirect regulation and cell-to-cell heterogeneity.

Micromanagement of Drosophila Post-Embryonic Development by Hox Genes

“…The Drosophila larval oenocytes are specialised cells that form in clusters beneath the developing epidermis, and play roles in the synthesis and metabolism of lipids and hydrocarbons (reviewed in [ 58 ]). It had previously been shown that binding of Abd-A to a rhomboid (rho) cis-regulatory module is required for the formation of larval oenocytes [ 59 , 60 ], this process was further investigated by Li-Kroeger and colleagues (2012) who discovered that complex interplay between Abd-A and its co-factors is required for the formation of these specialised cells [ 61 ]. In this context, it appears that Abd-A forms an activating complex composed of Hth, Exd and Pax2.…”

Mechanisms Underlying Hox-Mediated Transcriptional Outcomes

“…Intriguingly, Abd-A regulates these two CRMs in different cell types and in opposing ways. In the developing peripheral nervous system, Abd-A triggers the secretion of epidermal growth factor ligands from a specific subset of abdominal sensory organ precursor cells by activating the expression of the rhomboid ( rho ) serine protease gene via a highly conserved CRM called RhoA ( Brodu et al, 2002 ; Li-Kroeger et al, 2008 ). In contrast, Abd-A, as well as Ubx, suppresses leg development in abdominal segments by repressing the expression of the Distal-less ( Dll ) homeodomain protein in ectodermal cells via the Dll conserved regulatory element ( DCRE ) ( Vachon et al, 1992 ; Gebelein et al, 2002 , Gebelein et al, 2004 ).…”

“…First, the same Hox, Exd, and Hth binding sites are capable of mediating either activation or repression. The RhoA CRM contains a single set of adjacent Exd/Hth/Hox binding sites ( Figure 3B ; Brodu et al, 2002 ; Li-Kroeger et al, 2008 ), whereas the DCRE CRM contains three Hox sites, each of which is directly adjacent to a Exd or Hth site ( Figures 3C,E ; Gebelein et al, 2002 , Gebelein et al, 2004 ; Uhl et al, 2016 ). Each configuration of binding sites is capable of cooperatively binding Abd-A/Hth/Exd complexes.…”

Characterisation of the role and regulation of Ultrabithorax in sculpting fine-scale leg morphology

“…Hox genes also play more subtle but important post-embryonic roles in regulating cell identify to sculpt the fine-scale morphology of structures and organs, and consequently have been likened to “micromanagers” ( Akam, 1998a ; Akam, 1998b ; Hombría and Lovegrove, 2003 ; Buffry and McGregor, 2022 ). Several such post-embryonic roles of Hox genes have been identified in Drosophila ; for example, the specification of certain subtypes of cells in the central nervous system ( Kannan et al, 2010 ; Estacio-Gómez et al, 2013 ), the regulation of the development of larval oenocytes by abdominal-A ( abd-A ) ( Brodu et al, 2002 ), and the integration of regulatory information to specify differences in prothoracic (T1) leg bristle patterning among leg segments and between sexes by Sex-combs reduced ( Scr ) ( Eksi et al, 2018 ).…”