scholarly journals Early Head Specification in Xenopus laevis

2003 ◽  
Vol 3 ◽  
pp. 655-676
Author(s):  
Blue B. Lake ◽  
Kenneth R. Kao
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Neural Tube ◽  
Intracellular Signaling ◽  
Organizer Region ◽  
Dorsal Side ◽  
Bmp Signaling ◽  
The Body ◽  
Normal Brain ◽  
Sequence Of Events

The head represents the most dorsal and anterior extent of the body axis. InXenopus, the progressive determination of the head is an extremely complex process involving the activation and localized antagonism of a number of interdependent intracellular signaling pathways including the Wingless/Int-1 (Wnt), bone morphogenetic protein (BMP), and nodal-related pathways. The sequence of events that specify the head are: dorsal-ventral polarization and head organizer specification in the blastula; gastrulation; neural induction; and patterning of the anterior-posterior and dorsal-ventral neuraxes. Wnt signaling is required for the specification of the dorsal side initially but is then inhibited within the organizer once it has formed. Similarly, Wnt signaling is required along the length of the neural tube, but must be suppressed at its rostral end for normal brain development. Nodal signaling is also necessary for induction of the mesendoderm, but is subsequently suppressed in its dorsal-anterior extreme to specify head organizer. BMP signaling is required for ventral mesoderm and non-neural ectoderm, and must also be suppressed in the head organizer region and for the differentiation of the ventral midline of the neural tube. Thus, development of the head, and indeed the body plan in general, requires precisely timed and spatially restricted activation and repression of these signaling pathways.

scholarly journals Mechanism of CK2.3, a Novel Mimetic Peptide of Bone Morphogenetic Protein Receptor Type IA, Mediated Osteogenesis

2019 ◽  
Vol 20 (10) ◽  
pp. 2500 ◽  
Author(s):  
Vrathasha Vrathasha ◽  
Hilary Weidner ◽  
Anja Nohe
Keyword(s):  
Signaling Pathways ◽  
Treatment Options ◽  
Time Frame ◽  
Bmp Signaling ◽  
C2c12 Cells ◽  
Molecular Sequence ◽  
Sequence Of Events ◽  
Protein Receptor

Background: Osteoporosis is a degenerative skeletal disease with a limited number of treatment options. CK2.3, a novel peptide, may be a potential therapeutic. It induces osteogenesis and bone formation in vitro and in vivo by acting downstream of BMPRIA through releasing CK2 from the receptor. However, the detailed signaling pathways, the time frame of signaling, and genes activated remain largely unknown. Methods: Using a newly developed fluorescent CK2.3 analog, specific inhibitors for the BMP signaling pathways, Western blot, and RT-qPCR, we determined the mechanism of CK2.3 in C2C12 cells. We then confirmed the results in primary BMSCs. Results: Using these methods, we showed that CK2.3 stimulation activated OSX, ALP, and OCN. CK2.3 stimulation induced time dependent release of CK2β from BMPRIA and concurrently CK2.3 colocalized with CK2α. Furthermore, CK2.3 induced BMP signaling depends on ERK1/2 and Smad1/5/8 signaling pathways. Conclusion: CK2.3 is a novel peptide that drives osteogenesis, and we detailed the molecular sequence of events that are triggered from the stimulation of CK2.3 until the induction of mineralization. This knowledge can be applied in the development of future therapeutics for osteoporosis.

Genetic studies ofANKRD6as a molecular switch between Wnt signaling pathways in human neural tube defects

2014 ◽  
Vol 103 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Redouane Allache ◽  
Mingqin Wang ◽  
Patrizia De Marco ◽  
Elisa Merello ◽  
Valeria Capra ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Molecular Switch ◽  
Genetic Studies

scholarly journals Exercise-Induced Hypoglycemic Hemiplegia in a Child with Type 1 Diabetes: A Rare Find with Multiple Potential Causative Mechanisms

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
M. Constantine Samaan ◽  
Abeer Alassaf ◽  
Jonathan DellaVedova ◽  
Trisha Murthy
Keyword(s):  
Type 1 Diabetes ◽  
Motor Neurons ◽  
Intracellular Signaling ◽  
Rare Complication ◽  
Sudden Onset ◽  
The Body ◽  
Neurological Deficits ◽  
Oral Glucose ◽  
Normal Brain

A 10-year-old boy known to have type 1 diabetes presented to the emergency department with history of sudden onset of right-sided hemiplegia after exercise. He did not respond to oral glucose administration, but had an almost immediate resolution of symptoms with intravenous bolus of dextrose. Hemiplegic hypoglycemia is a rare complication in diabetic children, mostly affects the right side of the body, and is rarely recurrent. Children have normal brain imaging and angiography testing, and electroencephalogram may show slow-wave activity. The recovery takes place within 24 hours, and the prognosis is excellent with no focal neurological deficits noted. Our patient responded within minutes to intravenous dextrose, which is unusual and has not been reported previously. The mechanisms leading to development of hypoglycemic hemiplegia are unclear, but may involve effects of hypoglycemia on intracellular signaling pathways or molecules on motor neurons, as recent studies have shown normal brain cell glucose uptake and metabolism in hypoglycemia. While hypoglycemic hemiplegia is rare, it is a frightening experience to caregivers, and efforts should concentrate on its prevention by preventing hypoglycemia.

scholarly journals Spatiotemporal contribution of neuromesodermal progenitor-derived neural cells in the elongation of developing mouse spinal cord

2020 ◽  
Author(s):  
Mohammed R Shaker ◽  
Ju-Hyun Lee ◽  
Kyung Hyun Kim ◽  
Veronica Jihyun Kim ◽  
Joo Yeon Kim ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neural Tube ◽  
Dorsal Side ◽  
Lineage Tracing ◽  
The Body ◽  
Lumbar Spinal Cord ◽  
Genetic Lineage ◽  
Mouse Development ◽  
Axial Elongation

ABSTRACTDuring vertebrate development, the posterior end of the embryo progressively elongates in a head-to-tail direction to form the body plan. Recent lineage tracing experiments revealed that bi-potent progenitors, called neuromesodermal progenitors (NMPs), produce caudal neural and mesodermal tissues during axial elongation. However, their precise location and contribution to spinal cord development remain elusive. Here we used NMP-specific markers (Sox2 and BraT) and a genetic lineage tracing system to localize NMP progeny in vivo. NMPs were initially located at the tail tip, but were later found in the caudal neural tube, which is a unique feature of mouse development. In the neural tube, they produced neural stem cells (NSCs) and contributed to the spinal cord gradually along the AP axis during axial elongation. Interestingly, NMP-derived NSCs preferentially contributed to the ventral side first and later to the dorsal side at the lumbar spinal cord level, which may be associated with atypical junctional neurulation in mice. Our current observations detail the contribution of NMP progeny to spinal cord elongation and provide insights into how different species uniquely execute caudal morphogenesis.

scholarly journals Apcdd1 is a dual BMP/Wnt inhibitor in the developing nervous system and skin

2019 ◽  
Author(s):  
Alin Vonica ◽  
Neha Bhat ◽  
Keith Phan ◽  
Jinbai Guo ◽  
Lăcrimioara Iancu ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Bmp Signaling ◽  
Protein Domain ◽  
Axis Formation ◽  
Intercellular Signaling ◽  
Functional Protein ◽  
Animal Development ◽  
Bmp Receptors ◽  
Wnt Inhibitor

AbstractAnimal development and homeostasis depend on precise temporal and spatial intercellular signaling. Components shared between signaling pathways, generally thought to decrease specificity, paradoxically can also provide a solution to pathway coordination. Here we show that the Bone Morphogenetic Protein (BMP) and Wnt signaling pathways share Apcdd1 as a common inhibitor and that Apcdd1 is a taxon-restricted gene with novel domains and signaling functions. Previously, we showed that Apcdd1 inhibits Wnt signaling, here we find that Apcdd1 potently inhibits BMP signaling in body axis formation and neural differentiation in chicken, frog, zebrafish, and humans. Our results from experiments and modeling suggest that Apcdd1 may coordinate the outputs of two signaling pathways central to animal development and human disease.Significance StatementApcdd1 is a taxon-restricted gene that inhibits both BMP and Wnt intercellular signaling pathways in multiple organisms including mice, frog, zebrafish, and chicken. It encodes a bi-functional protein with a novel protein domain that can bind to Wnt and BMP receptors and block downstream signaling.

scholarly journals Runx1 is a central regulator of osteogenesis for bone homeostasis by orchestrating BMP and WNT signaling pathways

PLoS Genetics ◽  
2021 ◽  
Vol 17 (1) ◽  
pp. e1009233
Author(s):  
Chen-Yi Tang ◽  
Mengrui Wu ◽  
Dongfeng Zhao ◽  
Diep Edwards ◽  
Abigail McVicar ◽  
...  
Keyword(s):  
Bone Loss ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Skeletal Development ◽  
Bmp Signaling ◽  
Conditional Knockout ◽  
Sequencing Analysis ◽  
Bone Homeostasis ◽  
Promoter Regions

Runx1 is highly expressed in osteoblasts, however, its function in osteogenesis is unclear. We generated mesenchymal progenitor-specific (Runx1f/fTwist2-Cre) and osteoblast-specific (Runx1f/fCol1α1-Cre) conditional knockout (Runx1 CKO) mice. The mutant CKO mice with normal skeletal development displayed a severe osteoporosis phenotype at postnatal and adult stages. Runx1 CKO resulted in decreased osteogenesis and increased adipogenesis. RNA-sequencing analysis, Western blot, and qPCR validation of Runx1 CKO samples showed that Runx1 regulates BMP signaling pathway and Wnt/β-catenin signaling pathway. ChIP assay revealed direct binding of Runx1 to the promoter regions of Bmp7, Alk3, and Atf4, and promoter mapping demonstrated that Runx1 upregulates their promoter activity through the binding regions. Bmp7 overexpression rescued Alk3, Runx2, and Atf4 expression in Runx1-deficient BMSCs. Runx2 expression was decreased while Runx1 was not changed in Alk3 deficient osteoblasts. Atf4 overexpression in Runx1-deficient BMSCs did not rescue expression of Runx1, Bmp7, and Alk3. Smad1/5/8 activity was vitally reduced in Runx1 CKO cells, indicating Runx1 positively regulates the Bmp7/Alk3/Smad1/5/8/Runx2/ATF4 signaling pathway. Notably, Runx1 overexpression in Runx2-/- osteoblasts rescued expression of Atf4, OCN, and ALP to compensate Runx2 function. Runx1 CKO mice at various osteoblast differentiation stages reduced Wnt signaling and caused high expression of C/ebpα and Pparγ and largely increased adipogenesis. Co-culture of Runx1-deficient and wild-type cells demonstrated that Runx1 regulates osteoblast−adipocyte lineage commitment both cell-autonomously and non-autonomously. Notably, Runx1 overexpression rescued bone loss in OVX-induced osteoporosis. This study focused on the role of Runx1 in different cell populations with regards to BMP and Wnt signaling pathways and in the interacting network underlying bone homeostasis as well as adipogenesis, and has provided new insight and advancement of knowledge in skeletal development. Collectively, Runx1 maintains adult bone homeostasis from bone loss though up-regulating Bmp7/Alk3/Smad1/5/8/Runx2/ATF4 and WNT/β-Catenin signaling pathways, and targeting Runx1 potentially leads to novel therapeutics for osteoporosis.

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