Drosophila Genes in Development: Segment polarity gene family
hedgehog is a segment polarity gene in Drosophila; its biochemical and functional homolog in vertebrates is sonic hedgehog. It is a necessary element in the establishment of polarity during segmentation of the fly, and during the development of appendages.
Once segmentation is established (through the expression of pair rule genes), the anterior portion of each parasegment (the term for embryonic segments) takes on a different fate from the posterior portion. Segment polarity refers to this seeming polarization within each segment, resulting in differing cell fates. The requisite polarity in segments, ultimately responsible for proper development of Drosophila wings and legs, is established through the action of segment polarity genes.
The earliest action of hedgehog establishes the polarity of the 14 parasegments in the trunk (thorax and abdomen) of the fly, segments fated to develop into head, thorax and abdomen. Particularly interesting to developmental biologists is segmental specialization in the wing. The part of the embryo destined to become the adult wing is composed of the posterior part of parasegment 2, and the anterior part of parasegment 3. hedgehog, induced by Engrailed, is secreted by posterior cells (derived from the anterior part of parasegment 3) and diffuses a short distance. It acts on the adjacent (more anterior) segment to overcome repression by Patched and this results in the induction of decapentaplegic. DPP then defines the compartment border between the anterior and posterior halves of the wing (Zecca M., 1995).
Cyclic AMP-dependent protein kinase A (PKA) signals downstream to repress wingless and dpp.
In summary, hedgehog is a necessary element in the establishment of polarity during segmentation of the fly, and during the development of appendages. It is made by anterior compartments in the embryo (that become the posterior compartments of the developing adult). HH acts through Smoothened and Patched (probable components of the HH receptor). cAMP-dependent protein kinase A and Fused are the targets of SMO and PTC respectively. Signals from PKA and Fused integrate downstream of Fused to overcoming repression of target genes (wg and dpp) in adjacent compartments.
The HH protein has a novel sequence with a hydrophobic N-terminal region (Lee J. J., 1992 and Tashiro S., 1993).
Secreted
Hedgehog (Hh), a protein secreted by engrailed expressing Posterior (P) compartment cells, spreads into each Anterior (A) compartment across the anterior and the posterior boundaries to form opposing concentration gradients that organize cell pattern and polarity. Anteriorly and posteriorly situated cells within the A compartment respond in distinct ways to Hh: they express different combinations of genes and form different cell types.
Anterior compartment cells form polarized structures that, in the more anterior part of the compartment, point down the Hh gradient and, in the posterior part of the compartment, point up the gradient - therefore all structures point posteriorly. It has been shown that ectopic Hh can induce cells in the middle of each A compartment to activate en. Where this happens, A compartment cells are transformed into an ectopic P compartment and reorganize pattern and polarity both within and around the transformed tissue. Hh could pattern the A compartment by a simple gradient mechanism; the concentration of Hh would be read as a scalar to determine the type of cuticle secreted. Although this role is supported by the experiments in which Hh is ectopically expressed, there are some instances in which the slope of the presumed concentration gradient of Hh does not correspond with the orientation of hairs and bristles. Interestingly, only a subset of A compartment cells respond to ectopic Hh by activating engrailed and subsequently adopting a P identity. These cells occur in the middle of the A compartment, and therefore are not normally exposed to Hh secreted by the normal P compartment. It is clear that the A compartment is finely structured in terms of cell identity and fate (Struhl, 1997a).
Hh acts directly on A compartment cells to specify the various types of cuticular structures that they differentiate (Struhl, 1997b).
PKA and smo mutant clones in the anterior region of the A comparment alter cell type much as they do in the posterior portion, but some clones of smo cells in the A1 region form hairs that have reversed polarity and these hairs point anteriorly. Consequently, it is surmised that Hh influences cell polarity indirectly, possibly by inducing other signaling factors (Struhl, 1997b).
hh transcripts are expressed in embryos, larvae, pupae and adults with peaks of expression in 6-12hr embryos and early pupae. In embryos, hh transcripts are first expressed in a discrete pattern at the anterior and posterior ends of the embryo in the maxillary segment followed by a pattern of 14 parasegmental stripes. At germ band extension, a 15th stripe is seen. hh expression in the metameric portion of the embryo closely resembles en expression. The number of stripes gradually increases to 17. The terminal stripes are 2-3 cells wide and the internal stripes are 1 cell wide. Expression is also described in a variety of sites in the nonmetameric portion of the embryo including the intercalary and antennal segments, the procephalon, the gnathal segments, and portions of the hindgut. hh expression is pair-rule dependent. Expression is stronger in every second stripe and is stronger laterally than in dorsal and ventral regions. The expression in stripes reaches a maximum at stages 8-11. By the end of germband retraction, the stripes are situated in the posterior compartments of the lateral ectoderm. wg mutations caused diminished expression and ptc mutants cause expression in an ectopic stripe in each segment. nkd mutations cause broadening of the stripes. (Lee J.J., 1992 and Tashiro S., 1993)
1. [U59748] Human desert hedgehog (hDHH) mRNA, partial cds. 2. [U58511] Gallus gallus indian hedgehog protein mRNA, complete cds. 3. [Z11840] D.melanogaster hedgehog gene DNA. 4. [L02793] Drosophila melanogaster hedgehog protein (hh) gene, complete cds. 5. [L05404] Drosophila melanogaster hedgehog protein (hh) mRNA, complete cds. 6. [L05405] Drosophila melanogaster hedgehog protein (hh) gene, exon 1. 7. [S66384] hh=segment polarity gene hedgehog [Drosophila, Oregon-R, mRNA, 2305 nt]. 8. [L38517] Homo sapiens indian hedgehog protein (IHH) mRNA, 5' end. 9. [L38518] Homo sapiens sonic hedgehog protein (SHH) mRNA, complete cds. 10. [Z35669] B.rerio shh mRNA for sonic hedgehog protein. 11. [U30710] Danio rerio tiggy-winkle hedgehog (twhh), complete cds. 12. [U30711] Danio rerio sonic hedgehog (shh), complete cds. 13. [L35248] Xenopus laevis (clone fhh-4) hedgehog protein (vhh-1) mRNA, complete cds. 14. [L39213] Xenopus laevis morphogen (sonic hedgehog) mRNA, complete cds. 15. [U26314] Xenopus laevis sonic hedgehog mRNA, complete cds. 16. [U26349] Xenopus laevis cephalic hedgehog protein mRNA, complete cds. 17. [U26350] Xenopus laevis hedgehog protein 4 (hh4) mRNA, complete cds. 18. [U26404] Xenopus laevis banded hedgehog protein mRNA, complete cds.
Pair-rule
HOX-Pro