scholarly journals Tissue-specific regulation of BMP signaling by Drosophila N-glycanase 1

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Antonio Galeone ◽  
Seung Yeop Han ◽  
Chengcheng Huang ◽  
Akira Hosomi ◽  
Tadashi Suzuki ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Bmp Signaling ◽  
Global Developmental Delay ◽  
Tissue Specific ◽  
Specific Loss ◽  
Functional Conservation ◽  
Visceral Mesoderm ◽  
Evolutionarily Conserved ◽  
Specific Regulation ◽  
High Degree

Mutations in the human N-glycanase 1 (NGLY1) cause a rare, multisystem congenital disorder with global developmental delay. However, the mechanisms by which NGLY1 and its homologs regulate embryonic development are not known. Here we show that Drosophila Pngl encodes an N-glycanase and exhibits a high degree of functional conservation with human NGLY1. Loss of Pngl results in developmental midgut defects reminiscent of midgut-specific loss of BMP signaling. Pngl mutant larvae also exhibit a severe midgut clearance defect, which cannot be fully explained by impaired BMP signaling. Genetic experiments indicate that Pngl is primarily required in the mesoderm during Drosophila development. Loss of Pngl results in a severe decrease in the level of Dpp homodimers and abolishes BMP autoregulation in the visceral mesoderm mediated by Dpp and Tkv homodimers. Thus, our studies uncover a novel mechanism for the tissue-specific regulation of an evolutionarily conserved signaling pathway by an N-glycanase enzyme.

scholarly journals Author response: Tissue-specific regulation of BMP signaling by Drosophila N-glycanase 1

2017 ◽  
Author(s):  
Antonio Galeone ◽  
Seung Yeop Han ◽  
Chengcheng Huang ◽  
Akira Hosomi ◽  
Tadashi Suzuki ◽  
...  
Keyword(s):  
Bmp Signaling ◽  
Author Response ◽  
Tissue Specific ◽  
Specific Regulation

scholarly journals An evolutionarily conserved cis-regulatory element of Nkx3.2 contributes to early jaw joint morphology in zebrafish

2021 ◽  
Author(s):  
Jake Leyhr ◽  
Laura Waldmann ◽  
Beata Filipek-Górniok ◽  
Hanqing Zhang ◽  
Amin Allalou ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Regulatory Sequence ◽  
Enhancer Element ◽  
Functional Conservation ◽  
Evolutionarily Conserved ◽  
Joint Deformation ◽  
Jaw Joint ◽  
Enhancer Sequences ◽  
High Degree

The acquisition of movable jaws was a major event during vertebrate evolution. The role of NK3 homeobox 2 (Nkx3.2) transcription factor in patterning the primary jaw joint of gnathostomes (jawed vertebrates) is well known, however knowledge about its regulatory mechanism is lacking. In this study, we report a proximal enhancer element of Nkx3.2 that is deeply conserved in gnathostomes but undetectable in the jawless hagfish. This enhancer is active in the developing jaw joint region of the zebrafish Danio rerio, and was thus designated as jaw joint regulatory sequence 1 (JRS1). We further show that JRS1 enhancer sequences from a range of gnathostome species, including a chondrichthyan and mammals, have the same activity in the jaw joint as the native zebrafish enhancer, indicating a high degree of functional conservation despite the divergence of cartilaginous and bony fish lineages or the transition of the primary jaw joint into the middle ear of mammals. Finally, we show that deletion of JRS1 from the zebrafish genome using CRISPR/Cas9 leads to a transient jaw joint deformation and partial fusion. Emergence of this Nkx3.2 enhancer in early gnathostomes may have contributed to the origin and shaping of the articulating surfaces of vertebrate jaws.

scholarly journals Tissue-specific regulation of the alpha-myosin heavy chain gene promoter in transgenic mice.

1991 ◽  
Vol 266 (36) ◽  
pp. 24613-24620
Author(s):  
A. Subramaniam ◽  
W.K. Jones ◽  
J. Gulick ◽  
S. Wert ◽  
J. Neumann ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Gene Promoter ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Myosin Heavy Chain Gene ◽  
Tissue Specific ◽  
Specific Regulation

scholarly journals Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex

1998 ◽  
Vol 329 (1) ◽  
pp. 191-196 ◽  
Author(s):  
Melissa M. BOWKER-KINLEY ◽  
I. Wilhelmina DAVIS ◽  
Pengfei WU ◽  
A. Robert HARRIS ◽  
M. Kirill POPOV
Keyword(s):  
Tissue Distribution ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Pyruvate Dehydrogenase Kinase ◽  
Synthetic Analogue ◽  
Complex Activity ◽  
Acetyl Coa ◽  
Tissue Specific ◽  
Specific Regulation ◽  
Dehydrogenase Complex

Tissue distribution and kinetic parameters for the four isoenzymes of pyruvate dehydrogenase kinase (PDK1, PDK2, PDK3 and PDK4) identified thus far in mammals were analysed. It appeared that expression of these isoenzymes occurs in a tissue-specific manner. The mRNA for isoenzyme PDK1 was found almost exclusively in rat heart. The mRNA for PDK3 was most abundantly expressed in rat testis. The message for PDK2 was present in all tissues tested but the level was low in spleen and lung. The mRNA for PDK4 was predominantly expressed in skeletal muscle and heart. The specific activities of the isoenzymes varied 25-fold, from 50 nmol/min per mg for PDK2 to 1250 nmol/min per mg for PDK3. Apparent Ki values of the isoenzymes for the synthetic analogue of pyruvate, dichloroacetate, varied 40-fold, from 0.2 mM for PDK2 to 8 mM for PDK3. The isoenzymes were also different with respect to their ability to respond to NADH and NADH plus acetyl-CoA. NADH alone stimulated the activities of PDK1 and PDK2 by 20 and 30% respectively. NADH plus acetyl-CoA activated these isoenzymes nearly 200 and 300%. Under comparable conditions, isoenzyme PDK3 was almost completely unresponsive to NADH, and NADH plus acetyl-CoA caused inhibition rather than activation. Isoenzyme PDK4 was activated almost 2-fold by NADH, but NADH plus acetyl-CoA did not activate above the level seen with NADH alone. These results provide the first evidence that the unique tissue distribution and kinetic characteristics of the isoenzymes of PDK are among the major factors responsible for tissue-specific regulation of the pyruvate dehydrogenase complex activity.

Tissue-Specific Regulation of Genes by Estrogen Receptors

2012 ◽  
Vol 30 (01) ◽  
pp. 14-22 ◽  
Author(s):  
Dale Leitman ◽  
Sreenivasan Paruthiyil ◽  
Chaoshen Yuan ◽  
Candice Herber ◽  
Moshe Olshansky ◽  
...  
Keyword(s):  
Estrogen Receptors ◽  
Tissue Specific ◽  
Specific Regulation

scholarly journals Synaptic and epidermal accumulations of human acetylcholinesterase are encoded by alternative 3'-terminal exons.

1995 ◽  
Vol 15 (6) ◽  
pp. 2993-3002 ◽  
Author(s):  
S Seidman ◽  
M Sternfeld ◽  
R Ben Aziz-Aloya ◽  
R Timberg ◽  
D Kaufer-Nachum ◽  
...  
Keyword(s):  
Neuromuscular Junctions ◽  
Gene Transcript ◽  
Dna Encoding ◽  
Tissue Specific ◽  
Evolutionarily Conserved ◽  
Low Salt ◽  
Catalytically Active ◽  
Specific Accumulation ◽  
The Brain ◽  
Muscle Ache

Tissue-specific heterogeneity among mammalian acetylcholinesterases (AChE) has been associated with 3' alternative splicing of the primary AChE gene transcript. We have previously demonstrated that human AChE DNA encoding the brain and muscle AChE form and bearing the 3' exon E6 (ACHE-E6) induces accumulation of catalytically active AChE in myotomes and neuromuscular junctions (NMJs) of 2- and 3-day-old Xenopus embryos. Here, we explore the possibility that the 3'-terminal exons of two alternative human AChE cDNA constructs include evolutionarily conserved tissue-recognizable elements. To this end, DNAs encoding alternative human AChE mRNAs were microinjected into cleaving embryos of Xenopus laevis. In contrast to the myotomal expression demonstrated by ACHE-E6, DNA carrying intron 14 and alternative exon E5 (ACHE-I4/E5) promoted punctuated staining of epidermal cells and secretion of AChE into the external medium. Moreover, ACHE-E6-injected embryos displayed enhanced NMJ development, whereas ACHE-I4/E5-derived enzyme was conspicuously absent from muscles and NMJs and its expression in embryos had no apparent effect on NMJ development. In addition, cell-associated AChE from embryos injected with ACHE-I4/E5 DNA was biochemically distinct from that encoded by the muscle-expressible ACHE-E6, displaying higher electrophoretic mobility and greater solubility in low-salt buffer. These findings suggest that alternative 3'-terminal exons dictate tissue-specific accumulation and a particular biological role(s) of AChE, associate the 3' exon E6 with NMJ development, and indicate the existence of a putative secretory AChE form derived from the alternative I4/E5 AChE mRNA.

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