Kara Nordin

The F-box protein Ppa is a common regulator of core EMT factors Twist, Snail, Slug, and Sip1

The core EMT regulatory factors Twist, Snail, Slug, and Sip1, while structurally diverse, are coordinately regulated by a common E3 ubiquiting ligase, Ppa.

Shared regulatory programs suggest retention of blastula-stage potential in neural crest cells

From blastula to neural crest, do not pass go During vertebrate development, neural crest cells give rise to an unusual diversity of cells, including pigment cells, neurons, and cartilage. Traditionally, neural crest cells have been considered a derivative of neural ectoderm. Buitrago-Delgado et al. now show that neural crest cells have components of the molecular programs characteristic of blastula cells from earlier in development (see the Perspective by Hoppler and Wheeler). Blastula cells have the broad range of developmental potentials necessary to build the embryo. Neural crest cells may thus reflect persistence of the developmental programs characteristic of early development rather than re-specification of developmental programs after differentiation into neurectoderm. Science, this issue p. 1332; see also p. 1316 Neural crest cells may retain an embryonic expression program rather than reinventing it later. [Also see Perspective by Hoppler and Wheeler] Neural crest cells, which are specific to vertebrates, arise in the ectoderm but can generate cell types that are typically categorized as mesodermal. This broad developmental potential persists past the time when most ectoderm-derived cells become lineage-restricted. The ability of neural crest to contribute mesodermal derivatives to the bauplan has raised questions about how this apparent gain in potential is achieved. Here, we describe shared molecular underpinnings of potency in neural crest and blastula cells. We show that in Xenopus, key neural crest regulatory factors are also expressed in blastula animal pole cells and promote pluripotency in both cell types. We suggest that neural crest cells may have evolved as a consequence of a subset of blastula cells retaining activity of the regulatory network underlying pluripotency.Neural Crest cells, unique to vertebrates, are derived from the ectoderm but also generate mesodermal cell types. This broad developmental potential persists past the time when most ectoderm-derived cells have become lineage restricted. The ability of neural crest to contribute mesodermal derivatives to the bauplan has raised questions about how this apparent gain in developmental potential is achieved. Here we describe shared molecular underpinnings of potency in neural crest and blastula cells. We show that in Xenopus, key neural crest regulatory factors are also expressed in blastula animal pole cells and promote pluripotency in both cell types. We suggest that neural crest cells may have evolved as a consequence of a subset of blastula animal pole cells retaining activity of the regulatory network underlying pluripotency.

SUMOylated SoxE factors recruit Grg4 and function as transcriptional repressors in the neural crest

SUMOylation of SoxE alters its recruitment of transcriptional coregulatory factors, displacing the binding of coactivators and promoting the recruitment of the corepressor Grg4.

NEURODEVELOPMENT. Shared regulatory programs suggest retention of blastula-stage potential in neural crest cells.

From blastula to neural crest, do not pass go During vertebrate development, neural crest cells give rise to an unusual diversity of cells, including pigment cells, neurons, and cartilage. Traditionally, neural crest cells have been considered a derivative of neural ectoderm. Buitrago-Delgado et al. now show that neural crest cells have components of the molecular programs characteristic of blastula cells from earlier in development (see the Perspective by Hoppler and Wheeler). Blastula cells have the broad range of developmental potentials necessary to build the embryo. Neural crest cells may thus reflect persistence of the developmental programs characteristic of early development rather than re-specification of developmental programs after differentiation into neurectoderm. Science, this issue p. 1332; see also p. 1316 Neural crest cells may retain an embryonic expression program rather than reinventing it later. [Also see Perspective by Hoppler and Wheeler] Neural crest cells, which are specific to vertebrates, arise in the ectoderm but can generate cell types that are typically categorized as mesodermal. This broad developmental potential persists past the time when most ectoderm-derived cells become lineage-restricted. The ability of neural crest to contribute mesodermal derivatives to the bauplan has raised questions about how this apparent gain in potential is achieved. Here, we describe shared molecular underpinnings of potency in neural crest and blastula cells. We show that in Xenopus, key neural crest regulatory factors are also expressed in blastula animal pole cells and promote pluripotency in both cell types. We suggest that neural crest cells may have evolved as a consequence of a subset of blastula cells retaining activity of the regulatory network underlying pluripotency.Neural Crest cells, unique to vertebrates, are derived from the ectoderm but also generate mesodermal cell types. This broad developmental potential persists past the time when most ectoderm-derived cells have become lineage restricted. The ability of neural crest to contribute mesodermal derivatives to the bauplan has raised questions about how this apparent gain in developmental potential is achieved. Here we describe shared molecular underpinnings of potency in neural crest and blastula cells. We show that in Xenopus, key neural crest regulatory factors are also expressed in blastula animal pole cells and promote pluripotency in both cell types. We suggest that neural crest cells may have evolved as a consequence of a subset of blastula animal pole cells retaining activity of the regulatory network underlying pluripotency.

Sox5 Is a DNA-Binding Cofactor for BMP R-Smads that Directs Target Specificity during Patterning of the Early Ectoderm

The SoxD factor, Sox5, is expressed in ectodermal cells at times and places where BMP signaling is active, including the cells of the animal hemisphere at blastula stages and the neural plate border and neural crest at neurula stages. Sox5 is required for proper ectoderm development, and deficient embryos display patterning defects characteristic of perturbations of BMP signaling, including loss of neural crest and epidermis and expansion of the neural plate. We show that Sox5 is essential for activation of BMP target genes in embryos and explants, that it physically interacts with BMP R-Smads, and that it is essential for recruitment of Smad1/4 to BMP regulatory elements. Our findings identify Sox5 as the long-sought DNA-binding partner for BMP R-Smads essential to plasticity and pattern in the early ectoderm.

A transition from SoxB1 to SoxE transcription factors is essential for progression from pluripotent blastula cells to neural crest cells

The neural crest is a stem cell population unique to vertebrate embryos that gives rise to derivatives from multiple embryonic germ layers. The molecular underpinnings of potency that govern neural crest potential are highly conserved with that of pluripotent blastula stem cells, suggesting that neural crest cells may have evolved through retention of aspects of the pluripotency gene regulatory network (GRN). A striking difference in the regulatory factors utilized in pluripotent blastula cells and neural crest cells is the deployment of different sub-families of Sox transcription factors; SoxB1 factors play central roles in the pluripotency of naïve blastula and ES cells, whereas neural crest cells require SoxE function. Here we explore the shared and distinct activities of these factors to shed light on the role that this molecular hand-off of Sox factor activity plays in the genesis of neural crest and the lineages derived from it. Our findings provide evidence that SoxB1 and SoxE factors have both overlapping and distinct activities in regulating pluripotency and lineage restriction in the embryo. We hypothesize that SoxE factors may transiently replace SoxB1 factors to control pluripotency in neural crest cells, and then poise these cells to contribute to glial, chondrogenic and melanocyte lineages at stages when SoxB1 factors promote neuronal progenitor formation.

Shared Pluripotency Programs Suggest Derivation of Vertebrate Neural Crest from Blastula Cells

From blastula to neural crest, do not pass go During vertebrate development, neural crest cells give rise to an unusual diversity of cells, including pigment cells, neurons, and cartilage. Traditionally, neural crest cells have been considered a derivative of neural ectoderm. Buitrago-Delgado et al. now show that neural crest cells have components of the molecular programs characteristic of blastula cells from earlier in development (see the Perspective by Hoppler and Wheeler). Blastula cells have the broad range of developmental potentials necessary to build the embryo. Neural crest cells may thus reflect persistence of the developmental programs characteristic of early development rather than re-specification of developmental programs after differentiation into neurectoderm. Science, this issue p. 1332; see also p. 1316 Neural crest cells may retain an embryonic expression program rather than reinventing it later. [Also see Perspective by Hoppler and Wheeler] Neural crest cells, which are specific to vertebrates, arise in the ectoderm but can generate cell types that are typically categorized as mesodermal. This broad developmental potential persists past the time when most ectoderm-derived cells become lineage-restricted. The ability of neural crest to contribute mesodermal derivatives to the bauplan has raised questions about how this apparent gain in potential is achieved. Here, we describe shared molecular underpinnings of potency in neural crest and blastula cells. We show that in Xenopus, key neural crest regulatory factors are also expressed in blastula animal pole cells and promote pluripotency in both cell types. We suggest that neural crest cells may have evolved as a consequence of a subset of blastula cells retaining activity of the regulatory network underlying pluripotency.Neural Crest cells, unique to vertebrates, are derived from the ectoderm but also generate mesodermal cell types. This broad developmental potential persists past the time when most ectoderm-derived cells have become lineage restricted. The ability of neural crest to contribute mesodermal derivatives to the bauplan has raised questions about how this apparent gain in developmental potential is achieved. Here we describe shared molecular underpinnings of potency in neural crest and blastula cells. We show that in Xenopus, key neural crest regulatory factors are also expressed in blastula animal pole cells and promote pluripotency in both cell types. We suggest that neural crest cells may have evolved as a consequence of a subset of blastula animal pole cells retaining activity of the regulatory network underlying pluripotency.