High impact information on hb

• In C. elegans, a homolog of the well-known fly developmental regulator hunchback acts downstream of the microRNAs lin-4 and let-7 in a pathway controlling developmental timing [1].
• Hunchback is necessary and sufficient for first-born cell fates, whereas Krüppel is necessary and sufficient for second-born cell fates; this is observed in multiple lineages and is independent of the cell type involved [2].
• Based on the structure and genetic experiments, we identify putative interaction surfaces for hunchback mRNA and the cofactors Nanos and Brain Tumor. This analysis suggests that similar features in helical repeat proteins are used to bind extended peptides and RNA [3].
• Binding of pumilio to maternal hunchback mRNA is required for posterior patterning in Drosophila embryos [4].
• Sites in hb mRNA that mediate this repression, named nanos response elements (NREs), have been identified [4].

Biological context of hb

• Here we show that the Bcd gradient displays a high embryo-to-embryo variability, but that this noise in the positional information is strongly decreased ('filtered') at the level of hunchback (hb) gene expression [5].
• Activation appears to depend on cooperative interactions among bcd and hb proteins, since disrupting single binding sites cause catastrophic reductions in expression. gt is directly involved in the formation of the anterior border, although additional repressors may participate in this process [6].
• A 142 bp core fragment containing one low affinity hb and five medium to strong bcd protein binding sites drives gene expression in a Kr-like location in the centre of the embryo [7].
• We further demonstrate that while the amino-terminal domain is largely dispensable for cooperative binding to the hb enhancer element, it is preferentially required for cooperative binding to the kni enhancer element [8].
• These results suggest that the individual phases of hb transcription, which overlap temporally and spatially, contribute specific patterning functions in early embryogenesis [9].

Anatomical context of hb

• The function of the latter class appears to be linked to the secondary expression of hb in the parasegment 4 (PS4) stripe at blastoderm stage [10].
• In Clogmia hb expression deviates from that known in Drosophila in two main respects: (1) it shows an extended dorsal domain that is linked to the large serosa anlage, and (2) it shows a terminal expression in the proctodeal region [11].
• Hunchback is required for the specification of the early sublineage of neuroblast 7-3 in the Drosophila central nervous system [12].
• In Drosophila, the first temporal identity of most neural stem cells (neuroblasts) in the embryonic ventral nerve cord is specified by the transient expression of the transcription factor Hunchback [13].
• Using hb-promoter/lacZ fusion gene constructs in combination with germ line transformation, we have delimited a regulatory region for the 2.9-kb transcript to approximately 300 bp upstream of the site of transcription initiation and show that this region is sufficient to confer the full regulation by bcd [14].

Physical interactions of hb

• The products of the Drosophila gap genes hunchback and Krüppel bind to the hunchback promoters [15].
• We have recently shown that Bcd binds cooperatively to a hb enhancer element and proposed that cooperative DNA binding is facilitated by an interaction between Bcd molecules [16].
• Embryonic silencing is initiated by hb protein which binds to the silencers to repress Ubx, thereby defining the Ubx domain [17].
• These results imply that the Polycomb complex is not dependent on hunchback and suggest that the pattern of silencing reflects rather the state of activity of the gene at the time the Polycomb complex is formed [18].
• The PUMILIO (PUM) protein is thought to bind the NREs and thereby repress hb translation [19].

Regulatory relationships of hb

• hunchback has an anterior and posterior expression pattern in Drosophila [20] [21], [22]. In the anterior half of the embryo, hunchback shows a sharp on-off expression pattern and depends on Bcd [20], [21] and on its own self-regulation [21], [22]. It has been recently shown that hunchback sharpness is due to spatial bistability stemming from hb self-regulation [23]. The position of the hb pattern is controlled by Bicoid cooperative binding, but this mechanism itself is not sufficient to generate hb’s expression sharpness [23].
• Zygotic expression of hb is directly activated by the bcd gene product, leading to a subdivision of the embryo into an anterior half expressing zygotically provided hb protein and a posterior half that does not [24].
• We conclude that hb represses Ubx expression directly by binding to BRE and probably other Ubx regulatory elements [25].
• We show here that the abdominal cad domain is regulated by the hunchback (hb) gradient through repression at high concentrations and activation at low concentrations of HB protein [26].
• We demonstrate that posterior stripe boundaries are established by gap protein repressors unique to each stripe: h stripe 5 is repressed by the giant (gt) protein on its posterior border and h stripe 6 is repressed by the hunchback (hb) protein on its posterior border [27].
• Furthermore, the maintenance of hb expression in the GMC is regulated by the activity of Prospero (Pros), a transcription factor which asymmetrically segregates into the GMC during mitosis and inhibits Svp activity on both, the transcriptional and posttranscriptional level [28].

Other interactions of hb

• In contrast to the Bcd gradient, the hb expression pattern already includes the information about the scale of the embryo [5].
• A morphogenetic gradient of hunchback protein organizes the expression of the gap genes Krüppel and knirps in the early Drosophila embryo [24].
• By ensuring correct POU gene expression boundaries, hb and cas maintain temporal subdivisions in the cell-identity circuitry controlling CNS development [29].
• The repressor of the anterior Ubx expression is the gap gene hunchback (hb) [25].
• Zygotic caudal regulation by hunchback and its role in abdominal segment formation of the Drosophila embryo [26].

Analytical, diagnostic and therapeutic context of hb

• Complementation tests show that Rg-pbx and hb are allelic [30].
• Primer extension analysis and in situ hybridization experiments demonstrate that in adult Drosophila females, transcripts of the gap gene hunchback (hb) are produced only by the distal (P1) promoter and that this expression is largely restricted to the ovarian nurse cells [31].
• The analysis of germ line chimeras by transplantation of homozygous mutant pole cells shows that hb is already expressed during oogenesis [32].
• Extensive sequence analysis of the developmental gene hunchback and its 5' and 3' regulatory regions in Drosophila melanogaster, Drosophila virilis, Musca domestica, and Tribolium castaneum, using a variety of computer algorithms, reveals regions of high sequence simplicity probably generated by slippage-like mechanisms of turnover [33].

References