Expression of zebrafish nk2.2 is influenced by sonic hedgehog/vertebrate hedgehog-1 and demarcates a zone of neuronal differentiation in the embryonic forebrain

Development ◽  
1995 ◽  
Vol 121 (6) ◽  
pp. 1755-1768 ◽  
Author(s):  
K.A. Barth ◽  
S.W. Wilson
Keyword(s):  
Neuronal Differentiation ◽  
Sonic Hedgehog ◽  
Narrow Band ◽  
Ectopic Expression ◽  
Homeobox Genes ◽  
Boundary Zone ◽  
Spatial Regulation ◽  
Signalling Molecule ◽  
The Brain

We have isolated zebrafish nk2.2, a member of the Nk-2 family of homeobox genes. nk2.2 is expressed in a continuous narrow band of cells along a boundary zone demarcating the location at which two of the earliest nuclei in the brain differentiate. This band of cells is located within a few cell diameters of cells expressing the signalling molecule sonic hedgehog/vertebrate hedgehog-1 (shh/vhh-1). Injection of shh/vhh-1 RNA results in ectopic expression of nk2.2 and concomitant abnormalities in the forebrain and eyes. Moreover, cyclops mutant embryos, which initially lack neurectodermal expression of shh/vhh-1, show a concomitant lack of nk2.2 expression. Together, these results suggest a requirement of shh/vhh-1 protein for the spatial regulation of nk2.2 expression.

N-terminal fatty-acylation of sonic hedgehog enhances the induction of rodent ventral forebrain neurons

Development ◽  
2001 ◽  
Vol 128 (12) ◽  
pp. 2351-2363 ◽  
Author(s):  
Jhumku D. Kohtz ◽  
Hae Young Lee ◽  
Nicholas Gaiano ◽  
Joshua Segal ◽  
Evan Ng ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Ectopic Expression ◽  
Wild Type ◽  
Ganglionic Eminence ◽  
Fatty Acylation ◽  
Lateral Ganglionic Eminence ◽  
Ganglionic Eminences ◽  
Islet 1 ◽  
The Brain ◽  
Sequential Induction

The adult basal ganglia arise from the medial and lateral ganglionic eminences, morphologically distinct structures found in the embryonic telencephalon. We have previously shown that temporal changes in sonic hedgehog (Shh) responsiveness determine the sequential induction of embryonic neurons that populate the medial and lateral ganglionic eminences. In this report, we show that Shh-mediated differentiation of neurons that populate the lateral ganglionic eminence express different combinations of the homeobox-containing transcription factors Dlx, Mash1 and Islet 1/2. Furthermore, we show that N-terminal fatty-acylation of Shh significantly enhances its ability to induce the differentiation of rat E11 telencephalic neurons expressing Dlx, Islet 1/2 or Mash1. Recent evidence indicates that in utero injection of the E9.5 mouse forebrain with retroviruses encoding wild-type Shh induces the ectopic expression of Dlx2 and severe deformities in the brain. In this report, we show that Shh containing a mutation at the site of acylation prevents either of these phenotypes. These results suggest that N-terminal fatty-acylation of Shh may play an important role in Shh-dependent signaling during rodent ventral forebrain formation.

Ectopic Expression of the Maize Homeobox Genes ZmHox1a or ZmHox1b Causes Pleiotropic Alterations in the Vegetative and Floral Development of Transgenic Tobacco

1996 ◽  
Vol 8 (3) ◽  
pp. 349
Author(s):  
Barbel Uberlacker ◽  
Bettina Klinge ◽  
Wolfgang Werr
Keyword(s):  
Transgenic Tobacco ◽  
Floral Development ◽  
Ectopic Expression ◽  
Homeobox Genes

Dual action of sonic hedgehog on chondrocyte hypertrophy:retrovirus mediated ectopic sonic hedgehog expression in limb bud micromass culture induces novel cartilage nodules that are positive for alkaline phosphatase and type X collagen

1997 ◽  
Vol 110 (21) ◽  
pp. 2691-2701 ◽  
Author(s):  
N.S. Stott ◽  
C.M. Chuong
Keyword(s):  
Alkaline Phosphatase ◽  
Gene Family ◽  
Alcian Blue ◽  
Sonic Hedgehog ◽  
Ectopic Expression ◽  
Limb Bud ◽  
Blue Staining ◽  
Alcian Blue Staining ◽  
Type X Collagen ◽  
Chondrocyte Maturation

Members of the vertebrate hedgehog gene family (HH) are involved in patterning and modulation of differentiation. Recently it has been shown that ectopic expression of HH gene family members in vivo blocks chondrocyte maturation through activation of a parathyroid hormone related peptide (PTHrP) dependent negative regulatory loop in the perichondrium. However, the direct effect of HH on chondrocyte maturation has not been tested. Here, we studied the effect of retroviral overexpression of the chicken sonic hedgehog gene (Shh) on the growth and maturation of limb bud cells in micromass cultures. Shh is neither expressed nor required for the initiation of cellular condensation in normal micromass cultures. With Shh over-expression, micromass cultures developed novel tightly whorled nodules in addition to the normal Alcian Blue positive cartilage nodules. We characterized the new nodules and showed that they are strongly positive for alkaline phosphatase, enriched in type X collagen and weakly positive for Alcian Blue staining. Shh overexpression also increased cell proliferation, but this cannot account for the formation of the new nodules. This current study shows that misexpression of Shh in in vitro chondrogenic cultures promotes characteristics of hypertrophic chondrocytes. Thus HH has two complementary functions; a direct positive effect on chondrocyte hypertrophy in the absence of PTHrP pathway, and an indirect negative feedback loop through PTHrP to prevent other less differentiated chondrocytes from becoming hypertrophic. These two complementary actions of HH coordinate the progression of cartilage maturation.

Requirements of Lim1, a Drosophila LIM-homeobox gene, for normal leg and antennal development

Development ◽  
2000 ◽  
Vol 127 (20) ◽  
pp. 4315-4323 ◽  
Author(s):  
T. Tsuji ◽  
A. Sato ◽  
I. Hiratani ◽  
M. Taira ◽  
K. Saigo ◽  
...  
Keyword(s):  
Ectopic Expression ◽  
Homeobox Genes ◽  
Homeobox Gene ◽  
Homeodomain Protein ◽  
Border Cells ◽  
Null Mutant ◽  
Tarsal Segment ◽  
Segment Boundary ◽  
Leg Development ◽  
Antagonistic Interactions

During Drosophila leg development, the distal-most compartment (pretarsus) and its immediate neighbour (tarsal segment 5) are specified by a pretarsus-specific homeobox gene, aristaless, and tarsal-segment-specific Bar homeobox genes, respectively; the pretarsus/tarsal-segment boundary is formed by antagonistic interactions between Bar and pretarsus-specific genes that include aristaless (Kojima, T., Sato, M. and Saigo, K. (2000) Development 127, 769–778). Here, we show that Drosophila Lim1, a homologue of vertebrate Lim1 encoding a LIM-homeodomain protein, is involved in pretarsus specification and boundary formation through its activation of aristaless. Ectopic expression of Lim1 caused aristaless misexpression, while aristaless expression was significantly reduced in Lim1-null mutant clones. Pretarsus Lim1 expression was negatively regulated by Bar and abolished in leg discs lacking aristaless activity, which was associated with strong Bar misexpression in the presumptive pretarsus. No Lim1 misexpression occurred upon aristaless misexpression. The concerted function of Lim1 and aristaless was required to maintain Fasciclin 2 expression in border cells and form a smooth pretarsus/tarsal-segment boundary. Lim1 was also required for femur, coxa and antennal development.

DARPP-32 promoter directs transgene expression to renal thick ascending limb of loop of Henle

1995 ◽  
Vol 269 (4) ◽  
pp. F564-F570 ◽  
Author(s):  
S. Blau ◽  
L. Daly ◽  
A. Fienberg ◽  
G. Teitelman ◽  
M. E. Ehrlich
Keyword(s):  
Transgene Expression ◽  
Ectopic Expression ◽  
Medium Size ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Transcription Start Sites ◽  
Medullary Thick Ascending Limb ◽  
Spiny Neurons ◽  
Adult Kidney ◽  
The Brain

DARPP-32, a dopamine- and adenosine 3',5'-cyclic monophosphate (cAMP)-regulated inhibitor of protein phosphatase-1, is highly colocalized with neuronal and nonneuronal D1-type receptors. DARPP-32 concentration is enriched in the renal outer medulla and in the medium-size spiny neurons of the brain. In the ascending limb of the loop of Henle, DARPP-32 is phosphorylated following stimulation by dopamine and other first messengers, and in this form inhibits the activity of the Na(+)-K(+)-adenosinetriphosphatase pump. For functional analysis of the DARPP-32 promoter in the kidney, we characterized the murine gene. There are two groups of transcription start sites utilized in the brain, but the proximal set appears to be preferentially used in the kidney. In four of four lines of mice carrying a DARPP-32/lacZ transgene with 2.1 kb of 5'-flanking DNA, adult kidney lacZ transgene expression mimicked that of endogenous DARPP-32. There was no ectopic expression in peripheral organs. We conclude that the sequences necessary for direction of DARPP-32 expression to the medullary thick ascending limb are contained within this 2.1-kb fragment.

Reconstruction of the Audiogram Using Brain Stem Responses and High-Pass Noise Masking

1979 ◽  
Vol 88 (3_suppl) ◽  
pp. 1-20 ◽  
Author(s):  
Manuel Don ◽  
Jos J. Eggermont ◽  
Derald E. Brackmann
Keyword(s):  
Hearing Loss ◽  
Brain Stem ◽  
Narrow Band ◽  
Pure Tone Audiometry ◽  
Normal Hearing ◽  
Noise Masking ◽  
Specific Frequency ◽  
High Pass ◽  
The Brain ◽  
Air Conduction

Contributions to the brain stem electrical responses (BSER) presumably initiated from specific frequency regions of the cochlea with center frequencies similar to the major audiometric frequencies (0.5, 1, 2, 4, and 8 kHz) are derived by the application of a high-pass noise masking technique utilizing click stimuli. In normal hearing subjects, these derived narrow-band responses from the midfrequency regions (4, 2, and 1 kHz) can be recognized at click levels as low as 10 dB HL. For the frequency regions around 8 kHz and 0.5 kHz, these derived responses can be discerned at click levels of 30 dB HL and higher. When one uses the lowest click level at which these derived responses can be obtained from a given frequency region, the differences between a patient with a hearing loss and a normal hearing subject correlate well with the amount of hearing loss (air conduction) recorded by conventional pure tone audiometry. Use of the high-pass noise masking technique to reconstruct the audiogram may be of great potential value in assessing young children and other individuals who cannot or will not respond to conventional audiometry.

Autoregulation of Shh expression and Shh induction of cell death suggest a mechanism for modulating polarising activity during chick limb development

Development ◽  
2000 ◽  
Vol 127 (22) ◽  
pp. 4811-4823 ◽  
Author(s):  
J.J. Sanz-Ezquerro ◽  
C. Tickle
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Sonic Hedgehog ◽  
Limb Development ◽  
Retroviral Vector ◽  
Cellular Mechanism ◽  
Limb Bud ◽  
Drug Induced ◽  
Signalling Molecule ◽  
Vertebrate Limb

The polarising region expresses the signalling molecule sonic hedgehog (Shh), and is an embryonic signalling centre essential for outgrowth and patterning of the vertebrate limb. Previous work has suggested that there is a buffering mechanism that regulates polarising activity. Little is known about how the number of Shh-expressing cells is controlled but, paradoxically, the polarising region appears to overlap with the posterior necrotic zone, a region of programmed cell death. We have investigated how Shh expression and cell death respond when levels of polarising activity are altered, and show an autoregulatory effect of Shh on Shh expression and that Shh affects cell death in the posterior necrotic zone. When we increased Shh signalling, by grafting polarising region cells or applying Shh protein beads, this led to a reduction in the endogenous Shh domain and an increase in posterior cell death. In contrast, cells in other necrotic regions of the limb bud, including the interdigital areas, were rescued from death by Shh protein. Application of Shh protein to late limb buds also caused alterations in digit morphogenesis. When we reduced the number of Shh-expressing cells in the polarising region by surgery or drug-induced killing, this led to an expansion of the Shh domain and a decrease in the number of dead cells. Furthermore, direct prevention of cell death using a retroviral vector expressing Bcl2 led to an increase in Shh expression. Finally, we provide evidence that the fate of some of the Shh-expressing cells in the polarising region is to undergo apoptosis and contribute to the posterior necrotic zone during normal limb development. Taken together, these results show that there is a buffering system that regulates the number of Shh-expressing cells and thus polarising activity during limb development. They also suggest that cell death induced by Shh could be the cellular mechanism involved. Such an autoregulatory process based on cell death could represent a general way for regulating patterning signals in embryos.

Intronic enhancers control expression of zebrafish sonic hedgehog in floor plate and notochord

Development ◽  
1999 ◽  
Vol 126 (10) ◽  
pp. 2103-2116 ◽  
Author(s):  
F. Muller ◽  
B. Chang ◽  
S. Albert ◽  
N. Fischer ◽  
L. Tora ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Sonic Hedgehog ◽  
Screening Strategy ◽  
Floor Plate ◽  
T Box ◽  
Important Region ◽  
Signalling Molecule ◽  
Intron 1 ◽  
Wide Range ◽  
Enhancer Sequences

The signalling molecule Sonic hedgehog (Shh) controls a wide range of differentiation processes during vertebrate development. Numerous studies have suggested that the absolute levels as well as correct spatial and temporal expression of shh are critical for its function. To investigate the regulation of shh expression, we have studied the mechanism controlling its spatial expression in the zebrafish. We employed an enhancer screening strategy in zebrafish embryos based on co-injection of putative enhancer sequences with a reporter construct and analysis of mosaic expression in accumulated expression maps. Enhancers were identified in intron 1 and 2 that mediate floor plate and notochord expression. These enhancers also drive notochord and floor plate expression in the mouse embryo strongly suggesting that the mechanisms controlling shh expression in the midline are conserved between zebrafish and mouse. Functional analysis in the zebrafish embryo revealed that the intronic enhancers have a complex organisation. Two activator regions, ar-A and ar-C, were identified in intron 1 and 2, respectively, which mediate mostly notochord and floor plate expression. In contrast, another activating region, ar-B, in intron 1 drives expression in the floor plate. Deletion fine mapping of ar-C delineated three regions of 40 bp to be essential for activity. These regions do not contain binding sites for HNF3beta, the winged helix transcription factor previously implicated in the regulation of shh expression, indicating the presence of novel regulatory mechanisms. A T-box transcription factor-binding site was found in a functionally important region that forms specific complexes with protein extracts from wild-type but not from notochord-deficient mutant embryos.

Coexpression of the homeobox genes Distal-less and homothorax determines Drosophila antennal identity

Development ◽  
2000 ◽  
Vol 127 (2) ◽  
pp. 209-216 ◽  
Author(s):  
P.D. Dong ◽  
J. Chu ◽  
G. Panganiban
Keyword(s):  
Limb Development ◽  
Ectopic Expression ◽  
Homeobox Genes ◽  
Biochemical Properties ◽  
The Body ◽  
Critical Function ◽  
Genital Disc ◽  
Identity Based

The Distal-less gene is known for its role in proximodistal patterning of Drosophila limbs. However, Distal-less has a second critical function during Drosophila limb development, that of distinguishing the antenna from the leg. The antenna-specifying activity of Distal-less is genetically separable from the proximodistal patterning function in that certain Distal-less allelic combinations exhibit antenna-to-leg transformations without proximodistal truncations. Here, we show that Distal-less acts in parallel with homothorax, a previously identified antennal selector gene, to induce antennal differentiation. While mutations in either Distal-less or homothorax cause antenna-to-leg transformations, neither gene is required for the others expression, and both genes are required for antennal expression of spalt. Coexpression of Distal-less and homothorax activates ectopic spalt expression and can induce the formation of ectopic antennae at novel locations in the body, including the head, the legs, the wings and the genital disc derivatives. Ectopic expression of homothorax alone is insufficient to induce antennal differentiation from most limb fields, including that of the wing. Distal-less therefore is required for more than induction of a proximodistal axis upon which homothorax superimposes antennal identity. Based on their genetic and biochemical properties, we propose that Homothorax and Extradenticle may serve as antenna-specific cofactors for Distal-less.

scholarly journals Histone H2AX promotes neuronal health by controlling mitochondrial homeostasis

2019 ◽  
Vol 116 (15) ◽  
pp. 7471-7476 ◽  
Author(s):  
Urbain Weyemi ◽  
Bindu D. Paul ◽  
Deeya Bhattacharya ◽  
Adarsha P. Malla ◽  
Myriem Boufraqech ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Ectopic Expression ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Histone H2ax ◽  
Mitochondrial Homeostasis ◽  
Neurobehavioral Deficits ◽  
Mutant Cells ◽  
The Brain

Phosphorylation of histone H2AX is a major contributor to efficient DNA repair. We recently reported neurobehavioral deficits in mice lacking H2AX. Here we establish that this neural failure stems from impairment of mitochondrial function and repression of the mitochondrial biogenesis gene PGC-1α. H2AX loss leads to reduced levels of the major subunits of the mitochondrial respiratory complexes in mouse embryonic fibroblasts and in the striatum, a brain region particularly vulnerable to mitochondrial damage. These defects are substantiated by disruption of the mitochondrial shape in H2AX mutant cells. Ectopic expression of PGC-1α restores mitochondrial oxidative phosphorylation complexes and mitigates cell death. H2AX knockout mice display increased neuronal death in the brain when challenged with 3-nitropronionic acid, which targets mitochondria. This study establishes a role for H2AX in mitochondrial homeostasis associated with neuroprotection.

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