Mitogenic action of hypoxia upon cutaneous neuroepithelial cells in developing zebrafish

2017 ◽  
Vol 77 (6) ◽  
pp. 789-801 ◽  
Author(s):  
Benjamin W. Dean ◽  
Thalia J. Rashid ◽  
Michael G. Jonz
2019 ◽  
Vol 30 (16) ◽  
pp. 1900-1910 ◽  
Author(s):  
Arthur Marivin ◽  
Mikel Garcia-Marcos

Dishevelled-Associating Protein with a high frequency of LEucines (DAPLE) belongs to a group of unconventional activators of heterotrimeric G-proteins that are cytoplasmic factors rather than membrane proteins of the G-protein–coupled receptor superfamily. During neurulation, DAPLE localizes to apical junctions of neuroepithelial cells and promotes apical cell constriction via G-protein activation. While junctional localization of DAPLE is necessary for this function, the factors it associates with at apical junctions or how they contribute to DAPLE-mediated apical constriction are unknown. MPDZ is a multi-PDZ (PSD95/DLG1/ZO-1) domain scaffold present at apical cell junctions whose mutation in humans is linked to nonsyndromic congenital hydrocephalus (NSCH). DAPLE contains a PDZ-binding motif (PBM) and is also mutated in human NSCH, so we investigated the functional relationship between both proteins. DAPLE colocalized with MPDZ at apical cell junctions and bound directly to the PDZ3 domain of MPDZ via its PBM. Much like DAPLE, MPDZ is induced during neurulation in Xenopus and is required for apical constriction of neuroepithelial cells and subsequent neural plate bending. MPDZ depletion also blunted DAPLE-­mediated apical constriction of cultured cells. These results show that DAPLE and MPDZ, two factors genetically linked to NSCH, function as cooperative partners at apical junctions and are required for proper tissue remodeling during early stages of neurodevelopment.


Author(s):  
Ugomma C. Eze ◽  
Aparna Bhaduri ◽  
Maximilian Haeussler ◽  
Tomasz J. Nowakowski ◽  
Arnold R. Kriegstein

AbstractThe human cortex comprises diverse cell types that emerge from an initially uniform neuroepithelium that gives rise to radial glia, the neural stem cells of the cortex. To characterize the earliest stages of human brain development, we performed single-cell RNA-sequencing across regions of the developing human brain, including the telencephalon, diencephalon, midbrain, hindbrain and cerebellum. We identify nine progenitor populations physically proximal to the telencephalon, suggesting more heterogeneity than previously described, including a highly prevalent mesenchymal-like population that disappears once neurogenesis begins. Comparison of human and mouse progenitor populations at corresponding stages identifies two progenitor clusters that are enriched in the early stages of human cortical development. We also find that organoid systems display low fidelity to neuroepithelial and early radial glia cell types, but improve as neurogenesis progresses. Overall, we provide a comprehensive molecular and spatial atlas of early stages of human brain and cortical development.


1996 ◽  
Vol 85 (1) ◽  
pp. 157-162 ◽  
Author(s):  
Guillermo A. de León ◽  
John A. Grant ◽  
Crystal F. Darling

✓ The case of an infant with a peculiar tumorous malformation of the cerebellum is described. The tumor apparently developed as an exophytic, hypertrophic sprout of the inferior vermis. It had a monstrous appearance resembling a crab, with a metameric body and multiple pairs of limbs attached to the folia of both cerebellar hemispheres. Histologically, the lesion was formed by poorly differentiated neuroepithelial cells without any evidence of organization into nuclei, cortex, or fascicles. Clinically, the tumor behaved in an indolent manner and did not regrow after subtotal surgical resection. Because of its gross appearance and its biological behavior, this unusual hamartoblastomatous growth is readily distinguished from medulloblastoma. The morphology of the cerebellum in Lhermitte—Duclos disease is reviewed, and a new interpretation of its basic structure is proposed. This and other known types of cerebellar hypertrophy are different from the malformation in the present case.


1994 ◽  
Vol 83 (2) ◽  
pp. 197-208 ◽  
Author(s):  
Elena Cattaneo ◽  
Lorenzo Magrassi ◽  
Giorgio Butti ◽  
Laura Santi ◽  
Alessio Giavazzi ◽  
...  

Author(s):  
P.G. Bannerman ◽  
T.M. Oliver ◽  
Z. Xu ◽  
A. Shieh ◽  
D.E. Pleasure

2000 ◽  
Vol 20 (11) ◽  
pp. 3896-3905 ◽  
Author(s):  
Payal Soni ◽  
Montaha Lakkis ◽  
Matthew N. Poy ◽  
Mats A. Fernström ◽  
Sonia M. Najjar

ABSTRACT pp120 (Ceacam 1) undergoes ligand-stimulated phosphorylation by the insulin receptor, but not by the insulin-like growth factor 1 receptor (IGF-1R). This differential phosphorylation is regulated by the C terminus of the β-subunit of the insulin receptor, the least conserved domain of the two receptors. In the present studies, deletion and site-directed mutagenesis in stably transfected hepatocytes derived from insulin receptor knockout mice (IR−/−) revealed that Tyr1316, which is replaced by the nonphosphorylatable phenylalanine in IGF-1R, regulated the differential phosphorylation of pp120 by the insulin receptor. Similarly, the nonconserved Tyr1316 residue also regulated the differential effect of pp120 on IGF-1 and insulin mitogenesis, with pp120 downregulating the growth-promoting action of insulin, but not that of IGF-1. Thus, it appears that pp120 phosphorylation by the insulin receptor is required and sufficient to mediate its downregulatory effect on the mitogenic action of insulin. Furthermore, the current studies revealed that the C terminus of the β-subunit of the insulin receptor contains elements that suppress the mitogenic action of insulin. Because IR−/− hepatocytes are derived from liver, an insulin-targeted tissue, our observations have finally resolved the controversy about the role of the least-conserved domain of insulin and IGF-1Rs in mediating the difference in the mitogenic action of their ligands, with IGF-1 being more mitogenic than insulin.


Endocrinology ◽  
2004 ◽  
Vol 145 (3) ◽  
pp. 1473-1480 ◽  
Author(s):  
Souichi Oomizu ◽  
Kirti Chaturvedi ◽  
Dipak K. Sarkar

Abstract Estradiol is known to increase lactotropic cell proliferation, but estradiol susceptibility varies among human populations and among various strains of rats. We had reported that folliculostellate (FS) cells regulate estradiol’s mitogenic action on lactotropes; therefore, we studied their role in determining the susceptibility to estradiol in a high estradiol-responsive rat strain, Fischer 344 (F344), and in a low-responsive strain, Sprague Dawley (SD). Determination of total S-100-positive FS cells in the pituitary revealed that F344 rats have significantly more FS cells than do SD rats. Estradiol treatment did not change the number of FS cells in both F344 and SD rats. When cotransplanted with F344 pituitaries under the kidney capsule or cocultured with F344-derived lactotropes in vitro, FS cells derived from F344 rats increased estradiol’s mitogenic action. They also increased estradiol’s mitogenic action on SD-derived lactotropes in primary cultures. However, SD-derived FS cells failed to increase estrogen’s action on F344- or SD-derived lactotropes. The levels of basic fibroblast growth factor production and secretion by TGF-β3 and estradiol were much higher in F344-derived FS cells than in SD-derived FS cells. However, the lactotropes’ growth response to basic fibroblast growth factor was similar in both strains. These data suggest that cell-cell interaction between FS cells and lactotropes regulates estradiol’s mitogenic action on lactotropes and also determines lactotrope susceptibility to the steroid.


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