Top 15 articles on Hox function- Part I
Ever since the landmark Paper of Ed Lewis in Nature 1978 ,deciphering the Bithorax complex in Fruit fly Drosophila melanogaster ,a number of papers contributed significantly in our understanding hox gene function in Drosophila and other metazoans. Today we take a look at my Favourite 15 Hox articles ( mostly on Drosophila ) that helped understanding function of these master regulators.Remember this list doesn’t include articles related to regulation of Hox genes , but only about discovery and function of Hox genes.
1) No points for guessing correct,The list begins with milestone article from Edward B Lewis published in 1978 issue of Nature. Ed’s 1978 article about bithorax complex is a paradigm for genetic control of development. Information of 30 years of classical genetic work is mentioned in about six pages.In this work he describes about the Number ,function and origin of genes in Bithorax complex of Drosophila and also talks about famous polycomb, cbx and Pbx mutants. All these details were resulted from some really outstanding Genetic experiments.
A gene complex controlling segmentation in Drosophila.
Lewis EB.
Nature. 1978 Dec 7;276(5688):565-70.
2) This article again appeared in Nature Journal in 1984 dealing with discovery of Homeodomain. Walter Gehring’s lab observed repetitive DNA sequence in the genome of Drosophila ,that appears to be localised specifically in the genes of Antennapedia and Bithorax complexes.This repetitive segment was later named Homeodomain ,which was later found in all hox genes across animal kingdom and also in some Non Hox genes.This discovery of Homeodomain revolutionised the field of Hox genes and also paved path for a new field of biology “Evolutionary developmental Biology (evo-devo).
A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and bithorax complexes.
McGinnis W, Levine MS, Hafen E, Kuroiwa A, Gehring WJ.
Nature. 1984 Mar 29-Apr 4;308(5958):428-33.
3) Mark Peifer and Eric Wieschaus’s work on Extradenticle (exd) mutants ( Both Zygotic and maternal) gave us some very important insights about the specificity of Hox proteins. As all Hox preteins recognise almost similar nucleotides on DNA ,raising the problem of specificity in vivo. The findings of Peifer and Wieschaus’s that in embryos with reduced levels of extradenticle gene product, anterior and posterior segmental transformations occur, most probably affecting the hox proteins function.This work led to the idea that Hox proteins usually don’t act alone and co factors like exd play a significant role in attaining specificity.
Mutations in the Drosophila gene extradenticle affect the way specific homeo domain proteins regulate
segmental identity.
Mark Peifer and Eric Wieschaus.
GENES & DEVELOPMENT 4:1209-1223,1990.
4) Another excellent paper explaining the specificity problem of Hox proteins.It is well known that The
homeodomain proteins encoded by the Drosophila extradenticle gene and its mammalian homologues, the pbx genes, contribute to HOX specificity by cooperatively binding to DNA with HOX proteins. SIu-KwONG CHAN AND RICHARD S. MANN in their 1996 PNAS article present co-operative DNA binding model based on studies of labial(Hox)-extradenticle-DNA complex.According to this model ,Hox and exd bind to DNA(through their respective sites -which is separated by 4 nucleotides) as a heterodimer in a head-to-tail orientation and some classic biochemical experiments demonstrate that extradenticle prefers to bind cooperatively with different HOX proteins depending on subtle differences in the heterodimer binding site.
A structural model for a homeotic protein-extradenticle-DNA complex accounts for the choice of HOX protein in the heterodimer.
SIu-KwONG CHAN AND RICHARD S. MANN
Proc. Natl. Acad. Sci. USA Vol. 93, pp. 5223-5228, May 1996
5) After the discovery of exd as cofactor of Hox ,Richard mann’s lab presented another hox cofactor Homothorax (hth)through their findings published in cell 1997 issue.Rieckhof et al showed that hth is necessary for the nuclear localization of an essential HOX cofactor, Extradenticle (EXD), and encodes a homeodomain protein shares extensive identity with the product of Meis1.
Nuclear Translocation of Extradenticle Requires homothorax, which Encodes an Extradenticle-Related Homeodomain Protein.
Gabrielle E. Rieckhof, Fernando Casares, THyung Don Ryoo, Muna Abu-Shaar and Richard S. Mann
Cell, Vol. 91, 171–183, October 17, 1997.
The remaining 10 articles will be published soon in two more parts .
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