Abstract：
:Three-dimensional (3D) organoid models derived from human pluripotent stem cells provide a platform for studying human development and understanding disease mechanisms. Most studies that examine biallelic inactivation of the cell cycle regulator Retinoblastoma 1 (RB1) and the link to retinoblastoma is in mice, however, less is known regarding the pathophysiological role of RB1 during human retinal development. To study the role of RB1 in early human retinal development and tumor formation, we generated retinal organoids from CRISPR/Cas9-derived RB1-null human embryonic stem cells (hESCs). We showed that RB is abundantly expressed in retinal progenitor cells in retinal organoids and loss of RB1 promotes S-phase entry. Furthermore, loss of RB1 resulted in widespread apoptosis and reduced the number of photoreceptor, ganglion, and bipolar cells. Interestingly, RB1 mutation in retinal organoids did not result in retinoblastoma formation in vitro or in the vitreous body of NOD/SCID immunodeficient mice. Together, our work identifies a crucial function for RB1 in human retinal development and suggests that RB1 deletion alone is not sufficient for tumor development, at least in human retinal organoids.
journal_name
Dev Bioljournal_title
Developmental biologyauthors
Zheng C,Schneider JW,Hsieh Jdoi
10.1016/j.ydbio.2020.03.011subject
Has Abstractpub_date
2020-06-15 00:00:00pages
197-207issue
2eissn
0012-1606issn
1095-564Xpii
S0012-1606(20)30093-2journal_volume
462pub_type
杂志文章abstract：:Regulation of gene expression during early embryonic development in the rabbit was investigated by quantitative assay of firefly luciferase activity obtained by microinjection of three plasmid constructs using the regulatory region of polyomavirus promoter (PrPyV) with two different enhancer sequences (wild type or mu...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.1994.1188
更新日期：1994-07-01 00:00:00
abstract：:We have examined the response of bovine oocytes matured in vitro for 24 hr to parthenogenic activation using compounds that increase intracellular calcium (ionomycin) or inhibit protein phosphorylation (6-dimethylaminopurine, DMAP). Treatment with ionomycin alone caused resumption of meiosis (57.8 +/- 7.8%) but not pr...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.1994.1351
更新日期：1994-12-01 00:00:00
abstract：:Genome integrity in the developing germ line is strictly required for fecundity. In proliferating somatic cells and in germ cells, there are mitotic checkpoint mechanisms that ensure accurate chromosome segregation and euploidy. There is growing evidence of mitotic cell cycle components that are uniquely required in t...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2015.03.011
更新日期：2015-06-15 00:00:00
abstract：:The cellular mechanisms underlying the amazing ability of sea cucumbers to regenerate their autotomized intestines have been widely described by us and others. However, the signaling pathways that control these mechanisms are unknown. Previous studies have shown that Wnt homologs are upregulated during early intestina...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2019.10.005
更新日期：2020-02-01 00:00:00
abstract：:Previous studies have suggested a role of the homeodomain Six family proteins in patterning the developing vertebrate head that involves appropriate segmentation of three tissue layers, the endoderm, the paraxial mesoderm and the neural crest cells; however, the developmental programs and mechanisms by which the Six g...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2005.12.015
更新日期：2006-05-15 00:00:00
abstract：:The neural cell adhesion molecule (NCAM) is thought to play a role in the formation of the vertebrate nervous system. In mammals and chicken, it is known that more than 100 different forms of the NCAM protein can be generated by alternative splicing of one primary transcript and it is possible that these different for...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/0012-1606(92)90276-m
更新日期：1992-01-01 00:00:00
abstract：:To examine the role of postsynaptic activity in regulating the rate of neuromuscular synapse elimination, contractile activity of neonatal rabbit soleus muscles was decreased by chronic superfusion of alpha-bungarotoxin (alpha-BGT) over their surfaces. Superfusion was begun at 6 days postnatal and continued for a vari...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/s0012-1606(89)80009-0
更新日期：1989-02-01 00:00:00
abstract：:Actin dynamics are necessary at multiple steps in the formation of multinucleated muscle cells. BAR domain proteins can regulate actin dynamics in several cell types, but have been little studied in skeletal muscle. Here, we identify novel functions for the N-BAR domain protein, Bridging integrator 3 (Bin3), during my...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2013.07.004
更新日期：2013-10-01 00:00:00
abstract：:At gastrulation in the sea urchin embryo dramatic cell adhesion changes contribute to primary mesenchyme cell ingression movements and to cell rearrangements during archenteron invagination. At ingression, quantitative adhesion assays demonstrated previously that primary mesenchyme cells (PMCs) change their affinity f...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.1998.9165
更新日期：1999-03-01 00:00:00
abstract：:Metaphase II arrest of Xenopus oocyte is characterized by the presence of M-phase-promoting factor (MPF) and of a microtubular spindle, both of which are stable in the presence of protein synthesis inhibitors. We studied in vivo this equilibrium state that is settled during meiotic maturation. At time of germinal vesi...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.1997.8543
更新日期：1997-05-01 00:00:00
abstract：:The ciliated band of the Strongylocentrotus purpuratus embryo consists of a columnar epithelium, 3-5 cells wide, which gives rise to a small number of neuroblasts. It arises late in development, as a border separating the squamous epithelial cells of the oral and aboral ectoderm. To determine the lineage origins of th...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.1993.1313
更新日期：1993-12-01 00:00:00
abstract：:The accumulation of the mRNAs from four Strongylocentrotus purpuratus actin genes (the single muscle gene M, and three cytoskeletal genes CyI, CyIIIa, and CyIIIb) and of transcripts from an RNA polymerase III-transcribed repeated sequence family (SURF1) was followed throughout the early development of hybrid embryos o...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/0012-1606(88)90439-3
更新日期：1988-11-01 00:00:00
abstract：:Octopamine is an important neuroactive substance that modulates several physiological functions and behaviors of invertebrate species. Its biosynthesis involves two steps, one of which is catalyzed by Tyramine beta-hydroxylase enzyme (TBH). The Tbetah gene has been previously cloned from Drosophila melanogaster, and n...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2003.07.019
更新日期：2003-12-01 00:00:00
abstract：:The outstanding migration and differentiation capacities of neural crest cells (NCCs) have fascinated scientists since Wilhelm His described this cell population in 1868. Today, after intense research using vertebrate model organisms, we have gained considerable knowledge regarding the origin, migration and differenti...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2010.05.012
更新日期：2010-08-15 00:00:00
abstract：:Chick embryonic heart cell isolates and monolayer cultures were prepared from atria and ventricles at selected stages of cardiac development. The cardiac myocytes were assayed for myosin heavy chain (MHC) content using monoclonal antibodies (McAbs) specific in the heart for atrial (B-1), ventricular (ALD-19), or condu...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/0012-1606(86)90241-1
更新日期：1986-05-01 00:00:00
abstract：:The sub-division of the posterior-most territory of the neural plate results in the formation of two distinct neural structures, the hindbrain and the spinal cord. Although many of the molecular signals regulating the development of these individual structures have been elucidated, the mechanisms involved in delineati...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2015.12.025
更新日期：2016-02-15 00:00:00
abstract：:To examine the possible role of homeo box genes in murine development we have studied the structure and expression pattern of Hox-2.5, a newly isolated homeo box gene that maps to the left end of the mouse Hox-2 locus on chromosome 11. The sequence of the Hox-2.5 homeo box has been determined. It is highly homologous ...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/0012-1606(89)90056-0
更新日期：1989-06-01 00:00:00
abstract：:Myogenic precursors in adult skeletal muscle (satellite cells) are mitotically quiescent but can proliferate in response to a variety of stresses including muscle injury. To gain further understanding of adult myoblasts, we analyzed myogenesis of satellite cells on intact fibers isolated from adult rat muscle. In this...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.1994.1226
更新日期：1994-08-01 00:00:00
abstract：:We investigated the influence of the growth surface on the direction of Xenopus spinal neurite growth in the presence of a dc electric field of physiological magnitude. The direction of galvanotropism was determined by the substratum; neurites grew toward the negative electrode (cathode) on untreated Falcon tissue cul...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.1998.9039
更新日期：1998-11-15 00:00:00
abstract：:Previous work in our laboratory has shown that a 62- to 64-kDa protein was a major component of the perinuclear ring of manchettes fractionated from rat spermatids. Mass spectrometry analysis of this protein indicated the presence of a glycine-rich domain homologous to human keratin 9 (K9). Several antibodies to K9, r...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.2000.9911
更新日期：2000-11-15 00:00:00
abstract：:The outgrowth of motor axons to the developing pectoral fin of the Japanese medaka fish (Oryzias latipes) was investigated both in wildtype embryos and in the pectoral finless (pl) mutants in which adults are missing pectoral fins. Late in embryogenesis the pectoral fin is a simple limb which contains two antagonist m...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/0012-1606(91)90445-9
更新日期：1991-07-01 00:00:00
abstract：:The adult fungiform taste papilla is a complex of specialized cell types residing in the stratified squamous tongue epithelium. This unique sensory organ includes taste buds, papilla epithelium and lateral walls that extend into underlying connective tissue to surround a core of lamina propria cells. Fungiform papilla...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2013.07.022
更新日期：2013-10-01 00:00:00
abstract：:The thisbe (ths) gene encodes a Drosophila fibroblast growth factor (FGF), and mutant females are viable but sterile suggesting a link between FGF signaling and fertility. Ovaries exhibit abnormal morphology including lack of epithelial sheaths and muscle tissues that surround ovarioles. Here we investigated how FGF i...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2015.04.023
更新日期：2015-08-01 00:00:00
abstract：:During the development of locomotion circuits it is essential that motoneurons with distinct subtype identities select the correct trajectories and target muscles. In vertebrates, the generation of motoneurons and myelinating glia depends on Olig2, one of the five Olig family bHLH transcription factors. We investigate...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2012.06.027
更新日期：2012-09-15 00:00:00
abstract：:Spore germination is a defined developmental process that marks a critical point in the life cycle of Dictyostelium discoideum. Upon germination the environmental conditions must be conducive to cell growth to ensure survival of emerged amoebae. However, the signal transduction pathways controlling the various aspects...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.1998.8854
更新日期：1998-04-15 00:00:00
abstract：:The Drosophila salivary gland is a simple tubular organ derived from a contiguous epithelial primordium, which is established by the activities of the homeodomain-containing proteins Sex combs reduced (SCR), Extradenticle (EXD), and Homothorax (HTH). EGF signaling along the ventral midline specifies the salivary duct ...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/s0012-1606(03)00140-4
更新日期：2003-06-15 00:00:00
abstract：:We have tested the role of proteoglycans in the development of feather pattern by culturing 7-day-old embryonic chick skins on medium containing para-nitrophenyl-beta-D-xyloside (2 mM). Xylosides compete with core proteins of proteoglycans by acting as exogenous acceptors for the synthesis of glycosaminoglycans leadin...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/0012-1606(88)90199-6
更新日期：1988-05-01 00:00:00
abstract：:Cadherin-11 (cad-11) is a novel member of the cadherin family of cell adhesion molecules, having recently been identified by means of the polymerase chain reaction. To study the function and expression of this molecule, we cloned mouse, cad-11 cDNA. Transfection of L cells with cDNA led them to acquire a typical cadhe...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1006/dbio.1995.1149
更新日期：1995-05-01 00:00:00
abstract：:Cardiac troponin T (cTnT) is a component of the troponin (Tn) complex in cardiac myocytes, and plays a regulatory role in cardiac muscle contraction by anchoring two other Tn components, troponin I (TnI) and troponin C, to tropomyosin (Tm) on the thin filaments. In order to determine the in vivo function of cTnT, we c...
journal_title：Developmental biology
pub_type： 杂志文章
doi：10.1016/j.ydbio.2008.07.007
更新日期：2008-10-01 00:00:00
abstract：:Biologists have long recognized that dramatic bending of a cell sheet may be driven by even modest shrinking of the apical sides of cells. Cell shape changes and tissue movements like these are at the core of many of the morphogenetic movements that shape animal form during development, driving processes such as gastr...
journal_title：Developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.ydbio.2009.09.009
更新日期：2010-05-01 00:00:00
