Genetic control of morphogenesis - Hox induced organogenesis of the posterior spiracles

Abstract

The posterior spiracle has become one of the best systems to study how Hox genes control morphogenesis. Interaction of Abdominal-B (ABD-B) with dorso ventral and intrasegmental positional information leads to the local activation of ABD-B primary targets in the dorsal region of the eighth abdominal segment (A8). Primary targets pattern the spiracle subdividing it into two broad areas: external stigmatophore vs. internal spiracular chamber precursor cells. Primary targets then activate secondary targets and modulate the expression of signalling molecules in the spiracle primordium creating unique spiracle positional values. This genetic cascade activates the "realisator" genes that modulate the cell behaviours causing invagination, elongation and cell rearrangements responsible for spiracle morphogenesis. The spiracle realisators that have been identified to date correspond to cell adhesion proteins, cytoskeleton regulators and cell polarity molecules. Interestingly, these realisators localise to different apico-basal locations in the cell (RhoGEF apical, Crumbs subapical, E-cadherin in the adherens junction, RhoGAP basolateral). Therefore, the Hox anterior-posterior code is converted in the cell into apico-basal information required to implement the posterior spiracle morphogenetic program. We believe this may be a common characteristic for Hox induced organogenesis. KEY WORDS: posterior spiracles, ABD-B, Hox gene, morphogenesis, organogenesisHow undifferentiated cells make an organ in a precise location is one of the key questions in Developmental Biology. While certain organs are repeatedly formed along the body axis, others are localised in particular antero-posterior positions by the control of the transcription factors encoded by the Hox genes (also known as homeotic genes). Hox genes activate stable developmental programs that allow the formation of segment specific structures. These structures may consist of particular bones with their unique shapes or of specific organs. An example of Hox gene regulation in mammals is the skeletal structure with its variety of vertebrae shapes and associated ribs. A similar example in arthropods is the variety of leg appendages present along the anterior-posterior axis of the body. In the past fifteen years our laboratory has analysed the posterior spiracles of Drosophila as a model to understand how the morphogenesis of segment specific organs is controlled. Our studies range from the early primordium specification to its final differentiation, trying to find out how the specific behaviour of groups of cells is integrated to achieve the morphogenetic movements that shape the organ. This review summarizes the work of our laboratory and others in what is one of the most Int. J. Dev. Biol. 53: 1349-1358 (2009) Posterior spiracle development overviewThe posterior spiracles form the only external connexion of the tracheal respiratory system of the early Drosophila larva. The posterior spiracles are ectoderm-derived epithelial structures composed of two differe...

Cellular and molecular insights into Hox protein action

“…Modulating cell shape is another way to control single or collective cell migration and tissue remodelling, and Hoxb1b has recently been shown to regulate microtubule dynamics during the process of neural tube formation in zebrafish (Zigman et al, 2014). Hox proteins also directly regulate cell shape, cell-to-cell communication and signalling to properly delimit functional and morphological borders between vertebrate hindbrain segments (Prin et al, 2014), and the Drosophila Hox protein Abdominal B (AbdB) has been shown to coordinate the modifications in cell adhesion and cytoskeleton required for cell shape changes and invagination during development of the posterior spiracle, which constitutes the posterior end of the larval respiratory system (Castelli Gair Hombria et al, 2009). Hox proteins can also couple differentiation with morphogenesis, controlling cell fate decisions along differentiation lineages.…”

Hox Targets and Cellular Functions

“…A strict hierarchical architecture whereby Hox proteins regulate cellular functions through intermediate genes is probably not a general rule, although in some cases Hox genes seem to follow this regulatory structure ([111]; see below). Nevertheless, even in this case dual regulation, direct and indirect, of some realizator genes, cannot be excluded.…”

“…The role of Hox genes in regulating cell affinities may be mediated also by cadherins. In the posterior spiracles of the embryo, Abd-B regulates the expression of cadherins, which are probably needed to maintain cohesion of the tissue during the morphogenetic movements that results in spiracle development [111, 161]. …”

“…PS develop in the embryonic eighth abdominal segment (A8) during 6–13 h of development and their formation requires the coordination of several cellular processes including changes in cell shape, cell rearrangements, cell adhesion, and cell polarity. The combination of simple organization and relatively complex cellular mechanisms makes the PS a tractable model to study the basis of Hox-directed organ formation [111, 223]. …”

“…As this chamber is formed, the cells located at the outside, marked by the expression of the gene spalt ( sal ), surround those making the spiracular chamber, undergo extensive rearrangements, and develop the stigmatophore. During these processes there is no cell death or cell division [111, 223]. …”