Bithorax complex in Drosophila consists of three homeodomain encoding proteins : Ultrabithorax (Ubx), abdominal-A (abd-A) and Abdominal-B (Abd-B). The function of these bithorax genes is to pattern entire abdomen ( A1-A9 segments ) and a part of third thoracic segment ,which happens to be their normal expression domain in embryos. These Hox proteins are expressed within specific parasegments (PS) , anatomical units that include the posterior portion of one segment and the anterior portion of the adjacent segment.
But the problem is that we have only three proteins and they need to take care of almost ten segments , meaning each gene in the complex must function to specify multiple parasegment identities.
Question is how this can be achieved?
This will lead us to a real classic article by James Castelli-Gair and Mike Akam’s published in 1995 issue of Development journal , where they studied, the role of Ultrabithorax Hox protein in specifying parasegment 5 and 6.
How it is possible for only three genes in the bithorax complex (BX-C) to specify identities to many segments or para segments to be precised? We can suggest few mechanisms ,which might be used get the above desired result :
(1) different spatial and temporal patterns of expression of a BX-C gene
(2) threshold responses to different levels of expression of a BX-C gene
(3) parasegment-specific expression of different BXC protein isoforms and
(4) combinatorial control ,where other factors also help BX-C in determining the segment identity.
It is believed that usually these mechanisms dont function alone and and probably all work together to the functioning of the BX-C.
Authors focused specifically on Ultrabithorax (Ubx), because these parasegments (5 and 6 ) exhibit very different morphologies. Parasegment 5 produces a typically thoracic set of pattern elements, modifying the ground plan displayed by parasegment 4. Parasegment 6 consists of posterior compartment of the third thoracic segment (T3p), but also the anterior compartment of the first abdominal segment (A1a). The important thing to note is that the patterning of the epidermis and peripheral nervous system is very different from that in the thorax.
So to understand how can Ubx protein can specify the formation of such diverse body patterns? Authors by ruling out the other possible mechanims like combinatoraial action of both Ubx and Antennapedia hox genes and different protein isoforms of the Ubx gene in forming different segment types ( for more details about how they ruled out these mechanism please refer to the article through the link provided in the reference section), provides compelling evidence for different spatial and temporal patterns of expression of Ubx protein in generating dramatic different segments.
James Castelli-Gair and Mike Akam focus on three larval structures whose embryonic primordia can be visualized with molecular probes: the anterior spiracle, thoracic pit sense organs and the Keilin’s organs.
Understanding the fate of the anterior spiracle, thoracic pit sense organs is rather straight forward but Keilin’s organ presence at the boundaries between PS3 and PS4, PS4 and PS5, and PS5 and PS6 posses many questions. James and Akam found spatial and temporal regulation of Ubx is sufficient to explain the
parasegment-specific development of all three structures.
Anterior spiracles are normally seen in PS4, but are repressed in PS5 and PS6 by the expression of Ubx in the cells homologous to the normal position of the spiracle in PS4. Similar is the case of pit sense organs , which normally develop in PS3-5 and their repression in PS6 is correlated to presence of high levels of Ubx protein in those particular cells.
Each thoracic segments of the larva bears a pair of Keilin’s organs on ventral side. The second thoracic
segment limb primordium gives rise to three structures: the wing imaginal disc, the leg imaginal disc, and
a larval mechanosensory structure ,which is Keilinâ€™s organ. This primodia is marked by presence of distalless (dll) gene , a marker for limb primodia through out animal kingdom. Ubx represses both Keilin’s organ development and Dll expression at the posterior edge of PS6 , but fails to do so in at the anterior edge of PS6 or in PS5.
To unravel the mystery , authors ectopically expressed ubx gene ,under the control of heat shock promoter at various time points during development and also looked into details of endogenous Ubx protein expression ,at the stage when dll is turned on in embryo. Expression data clearly reveled that that cells from the anterior edges of PS5 and PS6 that initiate Dll expression ,at a time when Ubx is either absent from these cells, or present at very low levels . The levels of Ubx increases in anterior PS6 and PS5 only after dll expression is fully established. Heat shock experiments have demonstrated that dll is sensitive to Ubx repression only during early development , as suggested by experiments where Ubx is driven after 7 hours of development fail to repress dll in thoracic segments. To put it short Ubx must be repressed in the presumptive limb primordia to allow their establishment .
How the Hox gene Ultrabithorax specifies two different segments: the significance of spatial and temporal regulation within metameres.
Castelli-Gair J, Akam M.
Development. 1995 Sep;121(9):2973-82.
Distal-less functions in subdividing the Drosophila thoracic limb primordium.
Bolinger RA, Boekhoff-Falk G.
Dev Dyn. 2005 Mar;232(3):801-16