Homeotic genes in flies Sem 9.3.B.6 Animal Science
So far We have seen that identities of each segment is determined by various regulators of segment polarity genes In arthopods, and in flies, each segment has different morphology and function. What then determines which morphology is for what segment? Homeotic genes
Homeotic selector genes There are two regions of Drosophila chromosome 3 that contain most of these homeotic genes. They are organized in order of function. One region, the Antennapedia complex, contains the homeotic genes labial (lab), Antennapedia (Antp), sex combs reduced (scr), deformed (dfd), and proboscipedia (pb). The labial and deformed genes specify the head segments, while sex combs reduced and Antennapedia contribute to giving the thoracic segments their identities. The proboscipedia gene appears to act only in adults, but in its absence, the labial palps of the mouth are transformed into legs. The second region of homeotic genes is the bithorax complex. There are three protein-coding genes found in this complex: ultrabithorax (ubx), which is required for the identity of the third thoracic segment; abdominal A (abda) and Abdominal B (AbdB) genes, which are responsible for the segmental identities of the abdominal segments. The lethal phenotype of the triple-point mutant Ubx-, abda-, AbdB- is identical to that resulting from a deletion of the entire bithorax complex. The chromosome region containing both the Antennapedia complex and the bithorax complex is often referred to as the homeotic complex (Hom-C).
Homeotic selector genes
Expression pattern The anterior boundary of homeotic gene expression is ordered from SCR (most anterior to ANTP, UBX and ABD-B (most posterior). This order is matched by the linear arrangement of the corresponding genes along chromosome 3.
What is homeotic gene? Mutation of any one of these genes results in transformation of a segment of group of segments into another. Mutation of these genes DOES NOT change the number of segments, only the identity of the segments. They create segment differences by modifying a basic ancestral pattern The Hox genes contain a 180 bp conservated region: the homeobox The homeotic genes encode transcription factors of a class called homeodomain proteins. The homeodomain is a 60aa protein domain, which binds DNA. Hox genes bind DNA regulatory elements of their target genes in a specific combination so that the expression pattern in each of the different segments is unique.
Hierarchy of genes in Drosophila development Maternal factor Gap genes Development of the number of segments Pair rule genes Selector genes (Hox genes) Development of the features of the segments Realisator genes
How do they do it? A very complicated question Three possible regulation By segmentation and segment pattering genes By interaction between homeotic genes themselves Regulation by members of polycomb genes
Step 1? The activity of ftz determines a precise registration between homeotic gene expression and the fundamental metameric nature of the body plan by establishing high levels of gene expression of Scr in PS2, Antp in PS4 and Ubx in PS6
Step 2? The loss of function of a homeotic gene in the thorax or abdomen do not reveal much about the function of that gene but the function of the other homeotic gene(s) that have not been removed. In general, a homeotic gene tends to repress within its own segment the expression of other homeotic genes with more anterior domain That is Antp would repress Scr
Step 3? Polycomb group response elements (PREs) mediate the mitotic inheritance of gene expression programs and thus maintain determined cell fates. By default, PREs silence associated genes via the targeting of Polycomb group (PcG) complexes. Upon an activating signal, however, PREs recruit counteracting trithorax group (trxg) proteins, which in turn maintain target genes in a transcriptionally active state. They regulate all homeotic genes
The basic ancestral pattern
Expression of Hox genes in arthropods crustaceans Branchiopoda (Artemia, the brine-shrimp) Malacostracans (Lobsters, hermit crabs) Insects
Dorso-ventral patterning
What?
Gastrulation Remember this?
To reiterate dorsal amnioserosa dorsal ectoderm neuroectoderm ventral mesoderm Ventral furrow formation
At first
Then
Also oocyte nucleus 1-6 7 8 D migration of nucleus 10A D A + P - - microtubules anterior follicle cells posterior V V 8 1-6 10A - + - gurken expression in the oocyte gurken expression in the oocyte
Dorsal
Or
Or There is nothing to stop pipe at the ventral follicle cells, therefore..
In a nut shell
Or
Note
Cells with highest nuclear Dorsal levels become mesoderm
Zygotically expressed genes
Action of Dorsal protein in ventral cells
Action of Dorsal protein in ventral cells Updated at 9 th Ed Ventral Patterning
High affinity for promoter, Not much Dorsal needed to activate
Lower affinity for promoter, More Dorsal needed to activate
Snail repression of rhomboid creates domains with distinct gene expression patterns
Developmental biology Scott F. Gilbert & others