Allele Dmel\hkb²

General Information
Symbol	Dmel\hkb²	Species	D. melanogaster
Name		FlyBase ID	FBal0031494
Feature type	allele	Associated gene	Dmel\hkb

Allele class	loss of function allele, hypomorphic allele - genetic evidence
Mutagen	ethyl methanesulfonate
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
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FB2013_03
FB2013_02
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Nature of the Allele
Allele class	hypomorphic allele - genetic evidence (Casanova, 1990, Rehorn et al., 1996, Dittrich et al., 1997) loss of function allele (Weigel et al., 1990, Eldon and Pirrotta, 1991, De Iaco et al., 2006)
Mutagen	ethyl methanesulfonate (Weigel et al., 1990)
Mutations Mapped to the Genome

Type Location Additional Notes References
Associated Sequence Data
DDBJ / EMBL / GenBank	DNA sequence Protein sequence Name

UniProtKB/Swiss-Prot
UniProtKB/TrEMBL

Progenitor genotype
Nature of the lesion	Statement Reference Nucleotide substitution: G?A. The above mutation is in the third nucleotide of the start codon. (De Iaco et al., 2006)
Cytology
Phenotypic Data
Phenotypic Class
	lethal \| embryonic stage (Weigel et al., 1990)
Phenotype Manifest In
	adult labral sense organ (Schmidt-Ott et al., 1994) A-subperineurial glial cell (Bossing et al., 1996) B-subperineurial glial cell of abdomen (Bossing et al., 1996) CNS glial cell (De Iaco et al., 2006) dorsopharyngeal organ (Schmidt-Ott et al., 1994) embryonic/larval esophagus \| embryonic stage (Schmidt-Ott et al., 1994) embryonic/larval labral nerve (Schmidt-Ott et al., 1994) embryonic/larval midgut \| anterior \| embryonic stage (Weigel et al., 1990) embryonic/larval midgut \| embryonic stage \| posterior (Weigel et al., 1990) embryonic/larval salivary gland \| embryonic stage (Myat and Andrew, 2000) embryonic head (Weigel et al., 1990) embryonic visceral muscle (Wolfstetter et al., 2009) interneuron (Bossing et al., 1996) lateral ventral subperineurial glial cell (Bossing et al., 1996) motor neuron (Bossing et al., 1996) pharyngeal monoscolopidial chordotonal organ (Schmidt-Ott et al., 1994) presumptive embryonic salivary gland (Myat and Andrew, 2002) stomatogastric nervous system (Schmidt-Ott et al., 1994) visceral mesoderm (with hkb^gurt) (Wolfstetter et al., 2009)
Detailed Description
	Statement Reference hkb[gurt]/hkb[2] embryos show the visceral mesoderm defects seen in hkb[gurt] embryos. Stage 15-16 hkb[2] embryos have strong defects in the visceral muscle. (Wolfstetter et al., 2009) Glia are absent from the CNS of hkb² mutant embryos. (De Iaco et al., 2006) Mutant embryos have abnormal salivary glands; 3% have elongated, branched lumens, 30% have elongated, expanded lumens and 67% have short, narrow lumens (normal salivary glands have elongated, unbranched lumens). Mutant salivary gland cells have reduced apical areas at all stages of salivary gland formation. Constriction of the apical domain is not as coordinated in invaginating mutant cells as in wild-type cells and occurs over a wider region of the salivary gland placode than normal. Once internalised, the mutant cells do not expand their apical domains to the same extent as wild-type cells and many of the mutant internalised cells do not polarise in the proximal-distal direction (in contrast to wild type). In hkb² embryos, the cells in the centre of the salivary gland placode are the first to invaginate, in contrast to wild type, where the dorsal-posterior cells invaginate first. The dorsal-posterior cells of the placode do not invaginate in mutant embryos. Mutant salivary gland cells show ultrastructural abnormalities at the apical surface once they begin to invaginate; they have less microvilli at the apical surface and less apical membrane than wild-type cells. The apical domains of the internalised mutant cells also appear disorganised; the distance between the apex of the cell and the adherens junctions is greater than normal. (Myat and Andrew, 2002) The salivary gland placodes of hkb² embryos appear identical to wild type. The first gross morphological defect seen is the incorrect positioning of the site of internalisation; the first cells to invaginate are those in the middle of the placode (in contrast to wild type where the first cells to invaginate are in the dorsal-posterior region of the placode). The invaginating pit is a mixture of wedge-shaped cells with constricted apices and basal nuclei, and elongated cells with randomly positioned nuclei (in wild-type all invaginating cells are approximately the same length and are wedge-shaped with basal nuclei). The pit is wider and shallower than in wild type and appears to include more cells. The invaginating salivary glands are trapezoidal shaped. The order of invagination is disrupted; cells immediately surrounding the pits appear to change shape and invaginate simultaneously. All secretory cells are eventually internalised, but the salivary glands are positioned more anteriorly and lie closer to the ventral midline and the body wall than the salivary glands of wild-type embryos. The characteristic cigar-shaped tubes of wild-type salivary glands are never formed, but the mutant salivary glands fuse along the ventral midline, forming dome-shaped organs with a commen lumen. Once invagination of the secretory cells is complete, open pits remain, as in wild-type embryos. (Myat and Andrew, 2000) Most of the ectopic serotonergic cells and most of the wild-type serotonergic cells found in larvae derived from embryos expressing eg^Scer\UAS.cDa under the control of Scer\GAL4^sca-537.4 are missing if the larvae are also homozygous for hkb². (Dittrich et al., 1997) hkb² tll¹ double mutant embryos show twisted gastrulation. hkb² tld⁹ double mutant embryos undergo germband extension, but fail to undergo germband retraction. (Yip et al., 1997) The aCC and pCC neurons are normal in homozygotes, but interneurons of the neuroblast (NB) 1-1 lineage lie in an abnormally ventral position and have pathfinding defects, often having abnormal contralateral projections. The ipsilateral interneurons sometimes project anteriorly or in multiple longitudinal fascicles. The motoneuron which normally projects from the segmental nerve (SN) in the thorax either has no projection, a projection that terminates prematurely in the SN, or a projection into the anterior root of the intersegmental nerve. A large cell of unknown origin is sometimes seen close to the aCC and pCC neurons. All glial cells in the abdomen derived from NB 1-1 are missing, and appear to be replaced by extra neuronal cells. NB 2-2 produces the normal number, position and type of cells in homozygous embryos, but the interneurons and motoneurons derived from it show pathfinding defects; the interneuronal projections in the thorax often have small ectopic ispilateral extensions and the contralateral bundle is loosely fasciculated. The motoneurons in the thorax often leave the central nervous system (CNS) through the wrong fascicle and terminate just outside the CNS before reaching their target muscles. Abdominal interneurons and motoneurons of the NB 2-2 lineage also have pathfinding defects. (Bossing et al., 1996) Intermediate hkb allele. (Margolis et al., 1995) Oesophagus, stomatogastric nervous system, labral nerve, epiphysis, dorsopharyngeal organ and pharyngeal monoscolopidial chordotonal organ are deleted. (Schmidt-Ott et al., 1994) No effect on prd expression in embryo. (Gutjahr et al., 1993) In hkb² tll^g double mutant embryos the posterior border of gt stripe 4 retracts even less than in tll^g mutants. (Eldon and Pirrotta, 1991) Does not interact with RpII140^wimp maternal effect. (Parkhurst and Ish-Horowicz, 1991) Failure of head involution. Absence of anterior midgut. In 50% of embryos a small remnant of posterior midgut is present, in 50% there is no posterior midgut at all. (Weigel et al., 1990)
External Data
Linkouts
Interactions
	Show the genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Suppressor of
Statement Reference hkb²/hkb[+] is a suppressor \| partially of visible \| dominant phenotype of gcm^Pyx (Popkova et al., 2012)
Phenotype Manifest In
Suppressed by
Statement Reference hkb² has presumptive embryonic salivary gland phenotype, suppressible \| partially by klar^{Scer\UAS.T:Hsap\MYC}/Scer\GAL4^wg.PM (Myat and Andrew, 2002)
NOT suppressed by
Statement Reference hkb² has lateral cord glial cell phenotype, non-suppressible by gcm^+t5.6 (De Iaco et al., 2006)
Suppressor of
Statement Reference hkb²/hkb[+] is a suppressor \| partially of chaeta \| supernumerary phenotype of gcm^Pyx (Popkova et al., 2012) hkb² is a suppressor of serotonergic neuron \| ectopic phenotype of Scer\GAL4^sca-537.4, eg^Scer\UAS.cDa (Dittrich et al., 1997)
Other
Statement Reference hkb², srp³ has embryonic/larval midgut primordium phenotype (Ainsworth et al., 2000, Ainsworth et al., 2000) hkb², srp³ has embryonic Malpighian tubule phenotype (Ainsworth et al., 2000, Ainsworth et al., 2000) Scer\GAL4^sca-537.4, eg^Scer\UAS.cDa, hkb² has serotonergic neuron phenotype (Dittrich et al., 1997, Dittrich et al., 1997)
Additional Comments
Genetic Interactions
Statement Reference The gcm^+t5.6 transgene fails to rescue the absent glial phenotype of hkb² mutants. (De Iaco et al., 2006) hkb² h⁶⁷⁴ double mutant embryos form salivary glands that are morphologically identical to those of hkb² single mutants, although there is an increase in salivary glands that fail to internalise (from 0% in the single mutants to 19% in the double mutants). The salivary gland defects of hkb² embryos are partially rescued by expression of klar^{Scer\UAS.T:Hsap\MYC} under the control of Scer\GAL4^wg.PM; the percentage of salivary glands with normal, elongated lumens is increased from 7% to 27%. (Myat and Andrew, 2002) hkb² srp³ embryos lack the midgut and Malpighian tubules fail to be specified in the hind gut. (Ainsworth et al., 2000)
Xenogenetic Interactions
Statement Reference
Complementation & Rescue Data
Fails to complement	hkb^gurt (Wolfstetter et al., 2009)
Rescued by	hkb²/hkb¹ is rescued by hkb^tBa (Bronner et al., 1994)
Comments	hkb¹/hkb² heterozygous embryos can be rescued by the hkb^tBa construct, embryonic gut, ventral furrow and head involution is normal, labral derivatives are abnormal. 4% survive to adulthood, these flies cannot fly and fail to respond to optic stimuli. (Bronner et al., 1994)
Stocks ( 2 )
Bloomington	5457 hkb² p^p/TM3, p⁺ Sb¹
Kyoto	108249 hkb² p^p/TM3, p⁺ Sb¹
Notes on Origin
Discoverer	G.J. Anderson and K.V. Anderson.

Comments
	Isolated in a screen for mutations affecting head development. hkb² exhibits a more extreme phenotype than hkb¹. (Weigel et al., 1990)
External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 2 )
Reported As
Symbol Synonym	hkb² (Wang et al., 2006, Gresens and Cook, 2006.8.29, Abrams and Andrew, 2005, Wolfstetter et al., 2009, Sanders et al., 2008, Kuzin et al., 2011, Moore et al., 2009)
Name Synonym	huckebein² (Sanders et al., 2008)
Secondary FlyBase IDs

References ( 42 )

Generate a list of	All references relating to this allele ( 42 )

List References by type	Research paper ( 39 ) Personal communication to FlyBase ( 2 ) Abstract ( 1 )
Recent research papers ( 2 )
	Popkova et al., 2012, PLoS Genet. 8(12): e1003159 Polycomb controls gliogenesis by regulating the transient expression of the gcm/glide fate determinant. [FBrf0220515] Kuzin et al., 2011, Mech. Dev. 128(3-4): 165--177 Functional analysis of conserved sequences within a temporally restricted neural precursor cell enhancer. [FBrf0213297] Show all research papers ...

Allele Dmel\hkb2

Allele Dmel\hkb²