Hoxful Monsters

Its really heartening to read an article which has neatly designed genetic experiments because its not very often you come across such great genetic work.It surprised me a bit initially not see any biochemical evidence but I personally like this way, may be being a geneticist at heart.Latest issue of development contains an article from the group of Ernesto Sanchez herrero ( an exceptional geneticist) dealing with autoregulation of Hox gene Ultrabithorax (Ubx). Infact autoregulation of Ubx was known since early 90’s but not much was known about mechanism involved and inconsistent, intriguing behaviour due to over expression of Ubx.

Regulation and Autoregulation :

Hox genes encode for transcripton factors containing evolutionary conserved DNA binding domain called “homeodoamin”.These Hox genes are integral part of early embryonic development in Drosophila.The expression domains of Hox genes are set in the embryo by the activity of gap genes and with certain input from pair rule and segment polarity genes the expression is further refined.Hox genes are also known to their own expression, Hox gene deformed does it in a positive way in epidermis and CNS ,whereas Ubx Negatively.

Ernesto’s group genetically dissected out the mechanism of Ubx autoregulation and important results of their findings are listed below:

1) When excess of Ubx is expressed using UAS - GAL4 system , The exogenous Ubx shuts off transcription of endogenous Ubx permanently and ploycomb group of genes play a vital role is bringing this change.This indicates that Ubx is permanently gets inactivated by its own product in a polycomb dependent manner.

2) Over expression of Ubx using a gal4 line which is expressed transiently( like dpp) in haltere imaginal discs transforms haltere into wing like tissue and in the case of contantly expressing gal4 (Like apterous gal4) reduces the size of haltere, with no sign of transformation towards wing. This also answers why only some Gal4 are able to show transformation when Ubx is oerexpressed in haltere discs.

3) Like Ubx,Hox gene abd-A also permanently shuts off Ubx transcription ,but Abd-B Hox genes fails to repress Ubx transcription permanently. This feature was attributed to presence of UBDA motif in Ubx and abd-A and absent in ABd-B.

4) Analogous to Ubx ,posterior selector gene engrailed ,when over expressed permanently represses its own transcription and authors predicts similar mechanism like that of Ubx might be functioning involving Polycomb group of genes.

Looking for biochemical evidence for involvement of Polycomb genes and Ubx in silencing of Ubx transcription will be an interesting step but it may not be an easy experiment to perform in larval tissue.

There are many genes in development which are negatively regulated by thier own product like Drosophila Distalless,labial Hox gene, Suppressor of Hairless,Brinker,trithorax like ,Mouse Six3 and Xenopus Goosccoid.One interesting thing to look will be to see whether similar mechanism operate while regualtion of these important developmental genes. All these genes point out to one important aspect that many genes need to maintain stable levels of expression in development and over riding this control may be deleterious.
Reference:

Daniel L. Garaulet, David Foronda, Manuel Calleja, and Ernesto Sanchez-Herrero
Polycomb-dependent Ultrabithorax Hox gene silencing induced by high Ultrabithorax levels in Drosophila
Development 20 Aug 2008; doi: 10.1242/dev.025809