scholarly journals Multimodal Long Noncoding RNA Interaction Networks: Control Panels for Cell Fate Specification

Genetics ◽  
2019 ◽  
Vol 213 (4) ◽  
pp. 1093-1110 ◽  
Author(s):  
Keriayn N. Smith ◽  
Sarah C. Miller ◽  
Gabriele Varani ◽  
J. Mauro Calabrese ◽  
Terry Magnuson

Lineage specification in early development is the basis for the exquisitely precise body plan of multicellular organisms. It is therefore critical to understand cell fate decisions in early development. Moreover, for regenerative medicine, the accurate specification of cell types to replace damaged/diseased tissue is strongly dependent on identifying determinants of cell identity. Long noncoding RNAs (lncRNAs) have been shown to regulate cellular plasticity, including pluripotency establishment and maintenance, differentiation and development, yet broad phenotypic analysis and the mechanistic basis of their function remains lacking. As components of molecular condensates, lncRNAs interact with almost all classes of cellular biomolecules, including proteins, DNA, mRNAs, and microRNAs. With functions ranging from controlling alternative splicing of mRNAs, to providing scaffolding upon which chromatin modifiers are assembled, it is clear that at least a subset of lncRNAs are far from the transcriptional noise they were once deemed. This review highlights the diversity of lncRNA interactions in the context of cell fate specification, and provides examples of each type of interaction in relevant developmental contexts. Also highlighted are experimental and computational approaches to study lncRNAs.

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3175-3185 ◽  
Author(s):  
M.Q. Martindale ◽  
J.Q. Henry

The nemerteans belong to a phylum of coelomate worms that display a highly conserved pattern of cell divisions referred to as spiral cleavage. It has recently been shown that the fates of the four embryonic cell quadrants in two species of nemerteans are not homologous to those in other spiralian embryos, such as the annelids and molluscs (Henry, J. Q. and Martindale, M. Q. (1994a) Develop. Genetics 15, 64–78). Equal-cleaving molluscs utilize inductive interactions to establish quadrant-specific cell fates and embryonic symmetry properties following fifth cleavage. In order to elucidate the manner in which cell fates are established in nemertean embryos, we have conducted cell isolation and deletion experiments to examine the developmental potential of the early cleavage blastomeres of two equal-cleaving nemerteans, Nemertopsis bivittata and Cerebratulus lacteus. These two species display different modes of development: N. bivittata develops directly via a non-feeding larvae, while C. lacteus develops to form a feeding pilidium larva which undergoes a radical metamorphosis to give rise to the juvenile worm. By examining the development of certain structures and cell types characteristic of quadrant-specific fates for each of these species, we have shown that isolated blastomeres of the indirect-developing nemertean, C. lacteus, are capable of generating cell fates that are not a consequence of that cell's normal developmental program. For instance, dorsal blastomeres can form muscle fibers when cultured in isolation. In contrast, isolated blastomeres of the direct-developing species, N. bivittata do not regulate their development to the same extent. Some cell fates are specified in a precocious manner in this species, such as those that give rise to the eyes. Thus, these findings indicate that equal-cleaving spiralian embryos can utilize different mechanisms of cell fate and axis specification. The implications of these patterns of nemertean development are discussed in relation to experimental work in other spiralian embryos, and a model is presented that accounts for possible evolutionary changes in cell lineage and the process of cell fate specification amongst these protostome phyla.


Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1363
Author(s):  
Xiao Huang ◽  
Liyue Zhang ◽  
Shanshan Yang ◽  
Yongpu Zhang ◽  
Mingjiang Wu ◽  
...  

Gastrulation drives the establishment of three germ layers and embryonic axes during frog embryonic development. Mesodermal cell fate specification and morphogenetic movements are vital factors coordinating gastrulation, which are regulated by numerous signaling pathways, such as the Wnt (Wingless/Integrated), Notch, and FGF (Fibroblast growth factor) pathways. However, the coordination of the Notch and FGF signaling pathways during gastrulation remains unclear. We identified a novel helix–loop–helix DNA binding domain gene (Hes5.9), which was regulated by the FGF and Notch signaling pathways during gastrulation. Furthermore, gain- and loss-of-function of Hes5.9 led to defective cell migration and disturbed the expression patterns of mesodermal and endodermal marker genes, thus interfering with gastrulation. Collectively, these results suggest that Hes5.9 plays a crucial role in cell fate decisions and cell migration during gastrulation, which is modulated by the FGF and Notch signaling pathways.


2021 ◽  
pp. mbc.E21-06-0291
Author(s):  
Rebecca S. Moreci ◽  
Terry Lechler

Proper spindle orientation is required for asymmetric cell division and the establishment of complex tissue architecture. In the developing epidermis, spindle orientation requires a conserved cortical protein complex of LGN/NuMA/dynein-dynactin. However, how microtubule dynamics are regulated to interact with this machinery and properly position the mitotic spindle is not fully understood. Furthermore, our understanding of the processes that link spindle orientation during asymmetric cell division to cell fate specification in distinct tissue contexts remains incomplete. We report a role for the microtubule catastrophe factor KIF18B in regulating microtubule dynamics to promote spindle orientation in keratinocytes. During mitosis, KIF18B accumulates at the cell cortex, colocalizing with the conserved spindle orientation machinery. In vivo we find that KIF18B is required for oriented cell divisions within the hair placode, the first stage of hair follicle morphogenesis, but is not essential in the interfollicular epidermis. Disrupting spindle orientation in the placode, using mutations in either KIF18B or NuMA, results in aberrant cell fate marker expression of hair follicle progenitor cells. These data functionally link spindle orientation to cell fate decisions during hair follicle morphogenesis. Taken together, our data demonstrate a role for regulated microtubule dynamics in spindle orientation in epidermal cells. This work also highlights the importance of spindle orientation during asymmetric cell division to dictate cell fate specification. [Media: see text] [Media: see text]


Development ◽  
2002 ◽  
Vol 129 (4) ◽  
pp. 1027-1036 ◽  
Author(s):  
Tanja Novotny ◽  
Regina Eiselt ◽  
Joachim Urban

The Drosophila ventral nerve cord (VNC) derives from neuroblasts (NBs), which mostly divide in a stem cell mode and give rise to defined NB lineages characterized by specific sets of sequentially generated neurons and/or glia cells. To understand how different cell types are generated within a NB lineage, we have focused on the NB7-3 lineage as a model system. This NB gives rise to four individually identifiable neurons and we show that these cells are generated from three different ganglion mother cells (GMCs). The finding that the transcription factor Hunchback (Hb) is expressed in the early sublineage of NB7-3, which consists of the early NB and the first GMC (GMC7-3a) and its progeny (EW1 and GW), prompted us to investigate its possible role in NB7-3 lineage development. Our analysis revealed that loss of hb results in a lack of the normally Hb-positive neurons, while the later-born neurons (designated as EW2 and EW3) are still present. However, overexpression of hb in the whole lineage leads to additional cells with the characteristics of GMC7-3a-derived neurons, at the cost of EW2 and EW3. Thus, hb is an important determinant in specifying early sublineage identity in the NB7-3 lineage. Using Even-skipped (Eve) as a marker, we have additionally shown that hb is also needed for the determination and/or differentiation of several other early-born neurons, indicating that this gene is an important player in sequential cell fate specification within the Drosophila CNS.


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
John W Wizeman ◽  
Qiuxia Guo ◽  
Elliott M Wilion ◽  
James YH Li

We applied single-cell RNA sequencing to profile genome-wide gene expression in about 9400 individual cerebellar cells from the mouse embryo at embryonic day 13.5. Reiterative clustering identified the major cerebellar cell types and subpopulations of different lineages. Through pseudotemporal ordering to reconstruct developmental trajectories, we identified novel transcriptional programs controlling cell fate specification of populations arising from the ventricular zone and the rhombic lip, two distinct germinal zones of the embryonic cerebellum. Together, our data revealed cell-specific markers for studying the cerebellum, gene-expression cascades underlying cell fate specification, and a number of previously unknown subpopulations that may play an integral role in the formation and function of the cerebellum. Our findings will facilitate new discovery by providing insights into the molecular and cell type diversity in the developing cerebellum.


2018 ◽  
Vol 1 (4) ◽  
pp. e201700016 ◽  
Author(s):  
Dong-Woo Hwang ◽  
Anbalagan Jaganathan ◽  
Padmina Shrestha ◽  
Ying Jin ◽  
Nour El-Amine ◽  
...  

Neural cell fate specification is a multistep process in which stem cells undergo sequential changes in states, giving rise to particular lineages such as neurons and astrocytes. This process is accompanied by dynamic changes of chromatin and in transcription, thereby orchestrating lineage-specific gene expression programs. A pressing question is how these events are interconnected to sculpt cell fate. We show that altered chromatin due to loss of the chromatin remodeler Chd5 causes neural stem cell activation to occur ahead of time. This premature activation is accompanied by transcriptional derepression of ribosomal subunits, enhanced ribosome biogenesis, and increased translation. These untimely events deregulate cell fate decisions, culminating in the generation of excessive numbers of astrocytes at the expense of neurons. By monitoring the proneural factor Mash1, we further show that translational control is crucial for appropriate execution of cell fate specification, thereby providing new insight into the interplay between transcription and translation at the initial stages of neurogenesis.


2021 ◽  
Author(s):  
Rebecca S. Moreci ◽  
Terry Lechler

Proper spindle orientation is required for asymmetric cell division and the establishment of complex tissue architecture. In the developing epidermis, spindle orientation requires a conserved cortical protein complex of LGN/NuMA/dynein-dynactin. However, how microtubule dynamics are regulated to interact with this machinery and properly position the mitotic spindle is not fully understood. Furthermore, our understanding of the processes that link spindle orientation during asymmetric cell division to cell fate specification in distinct tissue contexts remains incomplete. We report a role for the microtubule catastrophe factor KIF18B in regulating microtubule dynamics to promote spindle orientation in keratinocytes. During mitosis, KIF18B accumulates at the cell cortex, colocalizing with the conserved spindle orientation machinery. In vivo we find that KIF18B is required for oriented cell divisions within the hair placode, the first stage of hair follicle morphogenesis, but is not essential in the interfollicular epidermis. Disrupting spindle orientation in the placode, using mutations in either KIF18B or NuMA, results in aberrant cell fate marker expression of hair follicle progenitor cells. These data functionally link spindle orientation to cell fate decisions during hair follicle morphogenesis. Taken together, our data demonstrate a role for regulated microtubule dynamics in spindle orientation in epidermal cells. This work also highlights the importance of spindle orientation during asymmetric cell division to dictate cell fate specification.


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