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FB2025_05,released December 11, 2025
l(3)neo56, Mrt, bar-3, Hg
Hedgehog N-terminal signaling domain and C-terminal autoprocessing domain - helps establish embryonic segmentation - a segment polarity intercellular signaling protein - cooperates with Frazzled to guide axons through a non-canonical signalling pathway - A local difference in Hedgehog signal transduction increases mechanical cell bond tension and biases cell intercalations along the Drosophila anteroposterior compartment boundary
Please see the JBrowse view ofDmel\hh for information on other features
To submit a correction to a gene model please use theContact FlyBase form
AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.
Gene model reviewed during 5.44
Gene model reviewed during 5.48
2.3 (northern blot)
2.4 (northern blot)
There is only one protein coding transcript and one polypeptide associated with this gene
471 (aa)
471 (aa); 52 (kD)
471 (aa); 52 (kD predicted)
Interacts with shf (PubMed:15691765). Interacts with ptc and CG5504/l(2)tid (PubMed:12783860).
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\hh using theFeature Mapper tool.
The testis specificity index was calculated from modENCODE tissue expression data byVedeleket al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).
Comment:rows G,H
hh RNA can be detected in ganglion mother cells at 72 hours after larval hatching (ALH), but not at 48 hours ALH.
hh is expressed strongly in the anterior escort cells, and weakly in the posterior escort cells
At early stage 11,hh expression extends from the posterior optic lobe into the anterior optic lobe. It becomes restricted to the posterior optic lobe at mid stage 11 and later localizes to Bolwig organ precursor cells in the ventral posterior optic lobe.hh is expressed in cells immediately anterior to the tracheal pits.
hh transcripts are expressed in embryos, larvae, pupae and adults with peaks of expression in 6-12hr embryos and early pupae. Transcripts are first detected in embryonic stage 5 in a few stripes at the anterior and posterior ends of the embryo. 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 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.
Peaks ofhh expression are observedin 2-10hr embryos and in pupae. In embryos,hh transcripts are firstexpressed in a discrete pattern in the maxillary segment followed by apattern of 14 parasegmental stripes. At germ band extension, a 15th stripeis seen.hh expression in the metameric portion of the embryo closelyresemblesen expression. Expression is also described in a variety ofsites in the nonmetameric portion of the embryo including the intercalaryand antennal segments, the procephalon, the gnathal segments, and portionsof the hindgut. Expression in imaginal discs is described for theassociatedEcollacZ insertion.hh expression is pair-rule dependent. Inftz mutants, expression in the even-numbered parasegments is missing.wg mutations caused diminished expression andptc mutants causeexpression in an ectopic stripe in each segment.nkd mutations causebroadening of the stripes.
hh transcripts are first detected at the cellular blastoderm stage in 17 segmental stripes. 14 of the stripes are one cell wide and extend from 10-70% egg length. There are two 3-cell-wide stripes at 5% and 75% egg length and a dorsal anterior spot at 97% egg length. The stripes appear asynchronously. Even parasegmentally-numbered stripes precede odd-numbered stripes and anterior stripes precede more posterior stripes. The stripes are activated around the entire circumference of the embryo but disappear from the amnioserosa and mesoderm after gastrulation. At stage 11, the stripes are located just posterior to the parasegmental furrow and are spaced one cell anterior to the tracheal pit in each segment. Stripes persist after germ band retraction and are located in the posteriormost portion of the lateral ectoderm of each segment.hh transcripts are also expressed in the fore- and hindguts following gastrulation and germ band extension as well as in the cephalic region of the embryo. Up to stage 10, the intensity of staining is heavier in the nucleus than in the cytoplasm. After stage 10, RNA staining is predominantly cytoplasmic.
At the cellular blastoderm stage,hh transcripts are located predominantly in a single stripe at 75% egg length with additional transcripts at the anterior tip and along the ventral side. At gastrulation,hh is expressed in 14 single-cell-wide stripes between 30% and 65% egg length. The stripes are coincident withen expression and occur in the cells of the posterior compartments. They appear in a characteristic order, even-numbered ones before odd-numbered ones and anterior ones before posterior ones.hh is also expressed in a block of cells at the anterior end and in wide stripes at 10% and 75% egg length.hh transcripts are expressed later in the foregut, pharynx, esophagus, hindgut, and salivary glands.hh transcripts are exressed in imaginal discs where they are localized to the posterior compartments. The differences betweenhh anden expression are noted.
JBrowse - Visual display of RNA-Seq signals
ViewDmel\hh in JBrowse3-78
3-79.6
3-81.2
Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please seeJBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
New stable cell line derived fromS2-unspecified : A stable S2 cell line was isolated that expresses thesmoIP fluorescence-based sensor under the control ofUAS and reproducibly responds tohh stimulation.
New stable cell line derived fromS2-unspecified : S2 cells stably expressinghh-N were obtained from the laboratory of J.Jiang.
New stable cell line derived fromS2-unspecified : S2 cells stably expressing an inducibleTag:MYC-taggedsmo transgene under the control of the metallothionein promoter (pMT-Myc-Smo) were created. S2 cells stably expressing the N-terminal fragment ofhhh protein (HhN) that is active for signaling were created.
New stable cell line derived fromS2-ThermoFischer : Stable S2 cell lines overexpressing an N-terminal fragment ofhh were generated.
One of 42 Drosophila genes identified as being most likely to reveal molecular and cellular mechanisms of nervous system development or plasticity relevant to human Mental Retardation disorders.
Cholesterol modification ofhh protein is necessary (in the embryonic epidermis) for its assembly in large punctate subcellular structures and apical sorting through the activity of thedisp protein. Movement of these specialized structures containinghh protein through the cellular field is contingent upon the activity ofttv.
The expression ofhh in the wing disc, once activated, is dependent onph-p,trx andbrm. This may be due to an element upstream of thehh transcriptional start site (hh-CMM) that can bindPc protein and is able to act as a cellular memory module (CMM) when placed upstream of a UAS sequence in reporter constructs.
Misexpression ofhh in the soma induces germ cells to migrate to inappropriate locations in the developing embryo.
hh may act as an attractive guidance cue in germ cell migration in the embryo.
Migration of all tracheal branches is absent or stalled inhh-mutant embryos.
hh acts as a somatic stem cell factor in the ovary.
Clones ofhh mutants in the peripodial membrane disrupt disc growth.
hh signalling from the peripodial membrane, but not from the disc proper, is required for eye disc patterning and growth.
Three EMS induced alleles were identified in a screen for mutations affecting commissure formation in the CNS of the embryo.
hh signalling, coming from the adjacent P compartments across both Anterior/Posterior and Posterior/Anterior boundaries in the abdomen, organizes the pattern of all the Anterior cells.
ptc protein normally bindshh gene product without any help of thesmo gene product, thoughsmo is also a part of the receptor complex that bindshh and transduces thehh signal. The mechanism of signal transduction may involvehh binding specifically toptc and inducing a conformational change leading to the release of latentsmo activity.
hh andspi bring about the concerted assembly of ommatidial and synaptic cartridge units, imposing the "neurocrystalline" order of the compound eye onto the post-synaptic target field.hh encodes an inductive signal that is transported along retinal axons from the developing eye, and induces the expression ofEgfr in post-synaptic precursor cells.
Mutants are isolated in an EMS mutagenesis screen to identify zygotic mutations affecting germ cell migration at discrete points during embryogenesis: mutants exhibit segment polarity pattern defects.
Each primordia of the genital disc (female genital, male genital and anal primordia) is divided into anterior and posterior compartments. Clonal phenotype of genes known to play compartment specific functions demonstrate the anterior/posterior patterning functions of these genes are conserved in the genital disc.
Genetic combinations with mutants ofnub cause additive phenotypes.
Clonal analysis demonstrateshh has two distinct functions: expression is required in the photoreceptor cells to drive the morphogenetic furrow and in additionhh secreted from cells at the posterior disc margin is absolutely required for the initiation of patterning and predisposes ommatidial precursor cells to enter ommatidial assembly later.
hh protein secreted by posterior compartment cells plays a key role in patterning the posterior portion of the anterior compartment in adult abdominal segments.
hh elicits signal transduction via a complex that includes the products of thefu,ci andcos genes. The complex binds with high affinity to microtubules in the absence ofhh protein, but not whenhh is present. The complex may facilitate signalling fromhh by governing access of theci product to the nucleus.
The affinity boundary that segregates A and P cells into adjacent but immiscible cell populations is to a large extent a consequence of localhh signalling, rather than a reflection of an intrinsic affinity difference between A and P cells.
The pattern of expression ofhh in the larval and adult abdomen has been analysed.
The function ofhh in morphogenetic furrow progression is indirect. Cells that cannot receive/transduce thehh signal (as insmo clones) are still capable of entering a furrow fate and differentiating normally. Howeverhh is required to promote furrow progression and regulate its rate of movement across the disc, since the furrow is delayed insmo clones.
Elevated levels ofci are sufficient to activatehh target genes, even in the absence ofhh activity.ci activates transcription in yeast by a GLI consensus-binding site and the zinc finger domain is sufficient for its target specificity. Results strongly support a role forci as the transcriptional activator that mediateshh signaling.
Cells in anterior compartments lackingci expresshh and adopt a posterior fate without expressingen. Increased levels ofci can induce the expression ofdpp independent ofhh. Expression ofci in anterior cells controls limb development by restrictinghh secretion to posterior cells and by conferring competence to respond tohh by mediating transduction of thehh signal.
hh,wg anddpp are required for the establishment of signaling centres that coordinate morphogenesis in the hindgut epithelium. Activation of these genes in the developing hindgut and foregut requiresfkh.hh andwg activities in the gut epithelial cells are required for the expression of the homeobox genebap in the ensheathing visceral mesoderm.
The secretedhh product regulates the temporal assembly of photoreceptor precursor cells into ommatidia in the eye and is transmitted along the retinal axons to serve as the inductive signal in the brain, triggering neurogenesis in the developing visual centers.hh acts in the first of two retinal axon-mediated steps in the assembly of lamina synaptic cartridges.
Thehh autoprocessing reaction proceeds via an internal thioester intermediate and results in a covalent modification that increases the hydrophobic character of the signalling domain and influences its spatial and subcellular distribution. Truncated, unprocessed amino terminal protein causes embryonic mispatterning, suggesting a role for autoprocessing in spatial regulation ofhh signalling.
Cholesterol is the lipophilic moiety covalently attached to the amino-terminal signalling domain during autoprocessing. The carboxy-terminal domain acts as an intramolecular cholesterol transferase.
hh andwg specify the identities of specific regions of the head capsule. During eye-antennal disc developmenthh andwg expression initially overlap, but subsequently segregate. This regional segregation is critical to head specification and is regulated byoc.oc is a candidatehh target gene during early eye-antennal disc development.
hh protein acts in the wing as a signal to instruct neighbouring cells to adopt fates appropriate to the region of the wing just anterior to the compartmental boundary. Some members of thetrx group genes are involved in the transcriptional regulation of genes in thehh signalling pathway during imaginal development,Pc group genes are not involved in this regulation pathway.
Ectopic expression of the amino-terminal half of thehh protein results in effects similar to those induced by the wild-type protein, altering the identity of cells of both the dorsal and ventral ectoderm of the developing embryo and of cells of the anterior compartment of the imaginal discs. Ectopic expression of a form of the protein in which the signal cleavage sequence is mutated has no effect on larval or adult development. Results suggest that all signaling activity of thehh protein is most likely to reside in the amino terminal fragment generated by autoproteolysis.
Ectopic expression ofhh produces ectopic furrows in the anterior eye disc. In addition to changes in cell shape the ectopic furrows are associated cell proliferation, cell cycle synchronisation and pattern formation, events that parallel normal furrow progression. Results propose that the morphogenetic furrow coincides with a transient boundary that coordinates growth and differentiation of the eye disc andhh is necessary and sufficient to propagate this boundary across the epithelium.
Pka-C1 is essential during limb development to prevent inappropriatedpp andwg expression. A constitutively active form ofMmus\Pkaca, can prevent inappropriatedpp andwg expression but does not interfere with their normal induction byhh. The basal activity ofPka-C1 imposes a block on the transcription ofdpp andwg andhh exerts its organizing influence by alleviating the block.
hh,wg andmys are required for epithelial morphogenesis during proventriculus organ development. The morphogenetic process is suppressed bydpp. These results identify a novel cell signalling centre in the foregut that operates through a distinct genetic circuitry in the midgut to direct the formation of a multiply folded organ from a simple epithelial tube.
hh pathway mutants induce ectopic morphogenetic furrows. Results show that ommatidial clusters are self-organising units whose polarity in one axis is determined by the direction of furrow progression and which can independently define the position of an equator without reference to the global coordinates of the eye disc.
en governs growth and patterning in both anterior and posterior wing compartments by controlling the expression of thehh anddpp products as well as the response of the cells to them.en activity programs wing cells to expresshh whereas the absence ofen activity programs them to respond tohh by expressingdpp. Consequently, posterior cells secretehh product and induce a stripe of neighboring anterior cells across the compartment boundary to secretedpp.dpp may exert its organizing influence by acting as a gradient morphogen in contrast tohh which appears to act principally as a short range inducer ofdpp.
Ectopic expression ofhh in the anterior compartment of the wing disc causes overgrowth and pattern duplications in both anterior and posterior compartments of the wing disc, similar to alterations seen with ectopicdpp expression. These results indicate thathh is acting as a regulator ofdpp expression anddpp acts as an organising molecule controlling growth and patterning in the wing imaginal disc.
Comparisons of early development to that in other insects have revealed conservation of some aspects of development, as well as differences that may explain variations in early patterning events.
hh gene product is involved in regulatingptc expression in both embryo and discs, through its role in regulating gene expression along the anterior-posterior compartment border.hh function establishes the proximodistal axis in discs.hh protein is secreted and can cross embryo parasegment borders and the anterior-posterior compartment border of imaginal discs to neighbouring cells that express neitheren norhh. In the embryohh regulation ofptc apparently facilitatesptc andwg expression. In the discshh regulation ofptc and other genes in the anterior compartment helps to establish the proximodistal axis. Cell-cell communication mediated byhh links the special properties of compartment borders with specification of the proximodistal axis in imaginal development.
Wild type activity of five segment polarity genes,wg,ptc,en,nkd andhh, can account for most of the ventral pattern elements in the embryo.wg is required for naked cuticle anden is required for the first row of denticles in each abdominal denticle belt. Remaining cell types are produced by different combinations of the five gene activities.wg generates the diversity of cell types within the segment but each specific cell identity depends on the activity ofptc,en,nkd andhh.hh anden contribute to the pattern independently.hh andptc show mutual suppression through opposing effects onwg expression.hh alters the competence of cells to respond towg signal.
Developing retinal cells drive the progression of morphogenesis using the products of the hh and dpp genes. Clonal analysis suggests that gene products act as diffusible signals. hh induces the expression of dpp, the primary mediator of furrow movement.
Segment polarity mutations cause stripes of abnormal patterning within sectors of the leg disc, which may be mediated by regional perturbations in growth.
The ptc and hh genes encode components of a signal transduction pathway that regulate the expression of wg transcription following its activation by pair rule genes, but most other aspects of wg expression are independent of ptc and hh. Maintenance of wg expression depends upon the activity of hh, which acts only on neighboring cells to maintain wg expression. Expression of wg in the absence of ptc depends on hh.
A hh-related gene family has been identified in the zebrafish. Over-expression of one member, sonic hedgehog, in fly embryos, can activate the hh-dependent pathway.
Many alleles of hh act as dominant alleles of gl.
Although hh is essential for wg function in segmentation, wg appears to be still capable of some action in hh's absence.
Probably encodes a secreted or transmembrane protein.
The pattern ofhh protein expression during embryonic development has been analysed.
hh has been isolated and characterised.
hh gene cloned by plasmid rescue, the encoded protein is targetted to the secretory pathway (consistant with the non-cell autonomous requirement for hedgehog in cuticular patterning) and is expressed coincidentally with engrailed in embryos and imaginal discs. Maintainance of hh expression is dependent upon other segment polarity genes including engrailed and wingless. The amino acid sequence shows no similarity to any known protein but hydropathy analysis highlights a prominent hydrophobic region.
Sequence analysis of hh indicates that the gene product contains a putative transmembrane domain which suggests that it may be localized at the cell surface and be involved in cell-cell communication.
hh gene cloned and the sequence suggests a membrane associated protein. Expression pattern analysed and found to coincide with that of en in the epidermis. Though initially independent of en, hh expression later becomes en-dependent.
hh cannot completely rescue the ptc phenotype when in double mutant combinations.
The role ofptc in positional signalling is permissive rather than instructive, its activity is required to suppresswg transcription in cells predisposed to expresswg. These cells receive an extrinsic signal, encoded byhh, that antagonises the repressive activity ofptc. Results suggest thatptc protein may be the receptor for thehh signal, implying that this is an usual mechanism of ligand-dependent receptor inactivation.
hh is essential for maintaining the normal pattern of ptc expression.
Role of hh in neurogenesis has been studied.
Adult eyes are small, narrow with about 150 facets, eye disc is small due to precursor cell defects.
Genetic mosaics were used to determine that hh is not autonomous at the level of the single cell.
hh mutants display segment polarity segmentation defects.
A segment polarity type of embryonic lethal. Homozygous embryos have the posterior naked portion of the ventral surface of each segment deleted and replaced by a mirror image of the anterior denticle belts. Embryos appear to lack segmental boundaries. In strong alleles, there is no obvious segmentation; the larvae are approximately 40% the length of the wild-type larvae and there is a lawn of denticles arranged in a number of whorls on the ventral surface as a result of loss of naked cuticle. In intermediate alleles, naked cuticle is also lost from the ventral region, but the lawn of denticles is arranged in segmental arrays in mirror-image symmetry. The weak alleles show fusions that delete the naked cuticle usually between abdominal segments 1 and 2 and 6, 7 and 8 (Mohler, 1988). Temperature shift experiments with a temperature-sensitive allele (viable and normal at 18oC, and mutant at 25oC) indicate two phases of hh activity at 25oC, the first during early embryogenesis (3-6 hr of development) and the second during the late larval and early pupal stages (4-7 days of development).
Source for merge of: hh l(3)neo56
Source for merge of: hh anon-WO0134654.19
Source for merge of hh anon-WO0134654.19 was sequence comparison ( date:051113 ).
