Temporally dynamic antagonism between transcription and chromatin compaction controls stochastic photoreceptor specification

AbstractStochastic mechanisms diversify cell fates during development. How cells randomly choose between two or more fates remains poorly understood. In the Drosophila eye, the random mosaic of two R7 photoreceptor subtypes is determined by expression of the transcription factor Spineless (Ss). Here, we investigated how cis-regulatory elements and trans factors regulate nascent transcriptional activity and chromatin compaction at the ss gene locus during R7 development. We find that the ss locus is in a compact state in undifferentiated cells. An early enhancer drives ss transcription in all R7 precursors to open the ss locus. In differentiating cells, transcription ceases and the ss locus stochastically remains open or compacts. In SsON R7s, ss is open and competent for activation by a late enhancer, whereas in SsOFF R7s, ss is compact and repression prevents expression. Our results suggest that a temporally dynamic antagonism, in which transcription drives decompaction and then compaction represses transcription, controls stochastic cell fate specification.

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Prdm8 regulates pMN progenitor specification for motor neuron and oligodendrocyte fates by modulating the Shh signaling response

Development ◽

10.1242/dev.191023 ◽

2020 ◽

Vol 147 (16) ◽

pp. dev191023 ◽

Cited By ~ 3

Author(s):

Kayt Scott ◽

Rebecca O'Rourke ◽

Austin Gillen ◽

Bruce Appel

Keyword(s):

Motor Neuron ◽

Cell Fate ◽

Motor Neurons ◽

Oligodendrocyte Precursor Cells ◽

Cell Fate Specification ◽

Cell Fates ◽

Shh Signaling ◽

Fate Specification ◽

The People ◽

Oligodendrocyte Precursor

ABSTRACTSpinal cord pMN progenitors sequentially produce motor neurons and oligodendrocyte precursor cells (OPCs). Some OPCs differentiate rapidly as myelinating oligodendrocytes, whereas others remain into adulthood. How pMN progenitors switch from producing motor neurons to OPCs with distinct fates is poorly understood. pMN progenitors express prdm8, which encodes a transcriptional repressor, during motor neuron and OPC formation. To determine whether prdm8 controls pMN cell fate specification, we used zebrafish as a model system to investigate prdm8 function. Our analysis revealed that prdm8 mutant embryos have fewer motor neurons resulting from a premature switch from motor neuron to OPC production. Additionally, prdm8 mutant larvae have excess oligodendrocytes and a concomitant deficit of OPCs. Notably, pMN cells of mutant embryos have elevated Shh signaling, coincident with the motor neuron to OPC switch. Inhibition of Shh signaling restored the number of motor neurons to normal but did not rescue the proportion of oligodendrocytes. These data suggest that Prdm8 regulates the motor neuron-OPC switch by controlling the level of Shh activity in pMN progenitors, and also regulates the allocation of oligodendrocyte lineage cell fates.This article has an associated ‘The people behind the papers’ interview.

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Modifications of cell fate specification in equal-cleaving nemertean embryos: alternate patterns of spiralian development

Development ◽

10.1242/dev.121.10.3175 ◽

1995 ◽

Vol 121 (10) ◽

pp. 3175-3185 ◽

Cited By ~ 1

Author(s):

M.Q. Martindale ◽

J.Q. Henry

Keyword(s):

Cell Fate ◽

Cell Lineage ◽

Cell Types ◽

Embryonic Cell ◽

Specific Cell ◽

Cell Fate Specification ◽

Cell Fates ◽

Developmental Potential ◽

Fate Specification ◽

Symmetry Properties

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.

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Nuclear beta-catenin is required to specify vegetal cell fates in the sea urchin embryo

Development ◽

10.1242/dev.126.2.345 ◽

1999 ◽

Vol 126 (2) ◽

pp. 345-357 ◽

Cited By ~ 31

Author(s):

C.Y. Logan ◽

J.R. Miller ◽

M.J. Ferkowicz ◽

D.R. McClay

Keyword(s):

Cell Fate ◽

Sea Urchin ◽

Beta Catenin ◽

Cell Fate Specification ◽

Cell Fates ◽

Cell Stage ◽

Animal Pole ◽

Fate Specification ◽

The Relationship ◽

Vegetal Cell

Beta-catenin is thought to mediate cell fate specification events by localizing to the nucleus where it modulates gene expression. To ask whether beta-catenin is involved in cell fate specification during sea urchin embryogenesis, we analyzed the distribution of nuclear beta-catenin in both normal and experimentally manipulated embryos. In unperturbed embryos, beta-catenin accumulates in nuclei that include the precursors of the endoderm and mesoderm, suggesting that it plays a role in vegetal specification. Using pharmacological, embryological and molecular approaches, we determined the function of beta-catenin in vegetal development by examining the relationship between the pattern of nuclear beta-catenin and the formation of endodermal and mesodermal tissues. Treatment of embryos with LiCl, a known vegetalizing agent, caused both an enhancement in the levels of nuclear beta-catenin and an expansion in the pattern of nuclear beta-catenin that coincided with an increase in endoderm and mesoderm. Conversely, overexpression of a sea urchin cadherin blocked the accumulation of nuclear beta-catenin and consequently inhibited the formation of endodermal and mesodermal tissues including micromere-derived skeletogenic mesenchyme. In addition, nuclear beta-catenin-deficient micromeres failed to induce a secondary axis when transplanted to the animal pole of uninjected host embryos, indicating that nuclear beta-catenin also plays a role in the production of micromere-derived signals. To examine further the relationship between nuclear beta-catenin in vegetal nuclei and micromere signaling, we performed both transplantations and deletions of micromeres at the 16-cell stage and demonstrated that the accumulation of beta-catenin in vegetal nuclei does not require micromere-derived cues. Moreover, we demonstrate that cell autonomous signals appear to regulate the pattern of nuclear beta-catenin since dissociated blastomeres possessed nuclear beta-catenin in approximately the same proportion as that seen in intact embryos. Together, these data show that the accumulation of beta-catenin in nuclei of vegetal cells is regulated cell autonomously and that this localization is required for the establishment of all vegetal cell fates and the production of micromere-derived signals.

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Cooperative recruitment of Yan to paired high affinity ETS sites organizes repression to confer specificity and robustness to cardiac cell fate specification

10.1101/205724 ◽

2017 ◽

Author(s):

Jean-François Boisclair Lachance ◽

Jemma L. Webber ◽

Ilaria Rebay

Keyword(s):

Cell Fate ◽

Binding Sites ◽

Gene Editing ◽

Regulatory Elements ◽

Cardiac Cell ◽

Cell Fate Specification ◽

Developmental Transitions ◽

Fate Specification ◽

High Affinity ◽

Necessary And Sufficient

AbstractCis regulatory elements (CREs) are defined by unique combinations of transcription factor binding sites. Emerging evidence suggests that the number, affinity and organization of sites play important roles in regulating enhancer output and ultimately gene expression. Here, we investigate how the cis-regulatory logic of a tissue-specific CRE responsible for even-skipped (eve) induction during cardiogenesis organizes the competing inputs of two ETS members, the activator Pointed (Pnt) and the repressor Yan. Using a combination of reporter gene assays and CRISPR-Cas9 gene editing, we show that Yan and Pnt have distinct preferences for affinity of sites. Not only does Yan prefer high affinity sites, but a tandem pair of such sites is necessary and sufficient for Yan to tune Eve expression levels in newly specified cardioblasts and to block ectopic Eve induction and cell fate specification in surrounding progenitors. Mechanistically, the cooperative Yan recruitment promoted by this conserved high affinity ETS pair not only biases Yan-Pnt competition at the specific CRE, but also organizes Yan repressive complexes in 3D across the eve locus. Taken together our results uncover a novel mechanism by which differential interpretation of CRE syntax by a competing repressor-activator pair can confer both specificity and robustness to developmental transitions.

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