Multiple delta genes and lateral inhibition in zebrafish primary neurogenesis

Development ◽  
1998 ◽  
Vol 125 (3) ◽  
pp. 359-370 ◽  
Author(s):  
C. Haddon ◽  
L. Smithers ◽  
S. Schneider-Maunoury ◽  
T. Coche ◽  
D. Henrique ◽  
...  
Keyword(s):  
Lateral Inhibition ◽  
Notch Signalling ◽  
Neural Plate ◽  
Primary Neurons ◽  
Mauthner Cell ◽  
Neural Fate ◽  
Competitive Mechanism ◽  
Neuroepithelial Cells ◽  
Drosophila Cells ◽  
Primary Neurogenesis

In Drosophila, cells are thought to be singled out for a neural fate through a competitive mechanism based on lateral inhibition mediated by Delta-Notch signalling. In tetrapod vertebrates, nascent neurons express the Delta1 gene and thereby deliver lateral inhibition to their neighbours, but it is not clear how these cells are singled out within the neurectoderm in the first place. We have found four Delta homologues in the zebrafish--twice as many as reported in any tetrapod vertebrate. Three of these--deltaA, deltaB and deltaD--are involved in primary neurogenesis, while two--deltaC and deltaD--appear to be involved in somite development. In the neural plate, deltaA and deltaD, unlike Delta1 in tetrapods, are expressed in large patches of contiguous cells, within which scattered individuals expressing deltaB become singled out as primary neurons. By gene misexpression experiments, we show: (1) that the singling-out of primary neurons, including the unique Mauthner cell on each side of the hindbrain, depends on Delta-Notch-mediated lateral inhibition, (2) that deltaA, deltaB and deltaD all have products that can deliver lateral inhibition and (3) that all three of these genes are themselves subject to negative regulation by lateral inhibition. These properties imply that competitive lateral inhibition, mediated by coordinated activities of deltaA, deltaB and deltaD, is sufficient to explain how primary neurons emerge from proneural clusters of neuroepithelial cells in the zebrafish.

scholarly journals Antagonism of EGFR and notch signalling in the reiterative recruitment of Drosophila adult chordotonal sense organ precursors

Development ◽  
1999 ◽  
Vol 126 (14) ◽  
pp. 3149-3157 ◽  
Author(s):  
P. zur Lage ◽  
A.P. Jarman
Keyword(s):  
Lateral Inhibition ◽  
Single Cells ◽  
Growth Factor Receptor ◽  
Sense Organ ◽  
Notch Signalling ◽  
Equivalence Group ◽  
Neural Fate ◽  
Epidermal Growth ◽  
Sensory Bristles ◽  
Proneural Cluster

The selection of Drosophila melanogaster sense organ precursors (SOPs) for sensory bristles is a progressive process: each neural equivalence group is transiently defined by the expression of proneural genes (proneural cluster), and neural fate is refined to single cells by Notch-Delta lateral inhibitory signalling between the cells. Unlike sensory bristles, SOPs of chordotonal (stretch receptor) sense organs are tightly clustered. Here we show that for one large adult chordotonal SOP array, clustering results from the progressive accumulation of a large number of SOPs from a persistent proneural cluster. This is achieved by a novel interplay of inductive epidermal growth factor-receptor (EGFR) and competitive Notch signals. EGFR acts in opposition to Notch signalling in two ways: it promotes continuous SOP recruitment despite lateral inhibition, and it attenuates the effect of lateral inhibition on the proneural cluster equivalence group, thus maintaining the persistent proneural cluster. SOP recruitment is reiterative because the inductive signal comes from previously recruited SOPs.

XBF-2 is a transcriptional repressor that converts ectoderm into neural tissue

Development ◽  
1998 ◽  
Vol 125 (24) ◽  
pp. 5019-5031 ◽  
Author(s):  
F.V. Mariani ◽  
R.M. Harland
Keyword(s):  
Dna Binding ◽  
Neural Development ◽  
Ectopic Expression ◽  
Transcriptional Repressor ◽  
Neural Plate ◽  
Binding Domain ◽  
Expression Cloning ◽  
Dna Binding Domain ◽  
Neural Fate ◽  
Striking Contrast

We have identified Xenopus Brain Factor 2 (XBF-2) as a potent neuralizing activity in an expression cloning screen. In ectodermal explants, XBF-2 converts cells from an epidermal to a neural fate. Such explants contain neurons with distinct axonal profiles and express both anterior and posterior central nervous system (CNS) markers. In striking contrast to X-ngnR-1a or X-NeuroD, ectopic expression of XBF-2 in Xenopus embryos results in an expansion of the neural plate to the ventral midline. The enlarged neural plate consists predominantly of undifferentiated neurons. XBF-2 lies downstream of the BMP antagonists noggin, cerberus, and gremlin since ectodermal explants expressing these molecules exhibit strong expression of XBF-2. While XBF-2 does not upregulate the expression of secreted neural inducers, it downregulates the transcription of BMP-4, an epidermal inducer. We show that XBF-2 acts as a transcriptional repressor and that its effects can be phenocopied with either the engrailed or hairy repressor domain fused to the XBF-2 DNA-binding domain. A fusion of the DNA-binding domain to the activator domain of VP16 blocks the effects of XBF-2 and prevents neural plate development in the embryo. This provides evidence that a transcriptional repressor can affect both regional neural development and neurogenesis in vertebrates.

The activity of neurogenin1 is controlled by local cues in the zebrafish embryo

Development ◽  
1997 ◽  
Vol 124 (22) ◽  
pp. 4557-4569 ◽  
Author(s):  
P. Blader ◽  
N. Fischer ◽  
G. Gradwohl ◽  
F. Guillemont ◽  
U. Strahle
Keyword(s):  
Motor Neurons ◽  
Zebrafish Embryo ◽  
Neural Plate ◽  
Dominant Negative ◽  
Regulatory Subunit ◽  
Primary Neurons ◽  
Helix Loop Helix ◽  
Induced Neurons ◽  
Ectopic Neurons ◽  
Local Cues

Zebrafish neurogenin1 encodes a basic helix-loop-helix protein which shares structural and functional characteristics with proneural genes of Drosophila melanogaster. neurogenin1 is expressed in the early neural plate in domains comprising more cells than the primary neurons known to develop from these regions and its expression is modulated by Delta/Notch signalling, suggesting that it is a target of lateral inhibition. Misexpression of neurogenin1 in the embryo results in development of ectopic neurons. Markers for different neuronal subtypes are not ectopically expressed in the same patterns in neurogenin1-injected embryos suggesting that the final identity of the ectopically induced neurons is modulated by local cues. Induction of ectopic motor neurons by neurogeninl requires coexpression of a dominant negative regulatory subunit of protein kinase A, an intracellular transducer of hedgehog signals. Moreover, the pattern of endogenous neurogenin1 expression in the neural plate is expanded in response to elevated levels of Hedgehog (Hh) signalling or abolished as a result of inhibition of Hh signalling. Together these data suggest that Hh signals regulate neurogenin1 expression and subsequently modulate the type of neurons produced by Neurogenin1 activity.

Delta-Notch signalling and the patterning of sensory cell differentiation in the zebrafish ear: evidence from the mind bomb mutant

Development ◽  
1998 ◽  
Vol 125 (23) ◽  
pp. 4637-4644 ◽  
Author(s):  
C. Haddon ◽  
Y.J. Jiang ◽  
L. Smithers ◽  
J. Lewis
Keyword(s):  
Cell Differentiation ◽  
Lateral Inhibition ◽  
Hair Cells ◽  
Sensory Cell ◽  
Cell Types ◽  
Notch Signalling ◽  
Supporting Cells ◽  
Fine Grained ◽  
Mechanosensory Hair Cells ◽  
The Mind

Mechanosensory hair cells in the sensory patches of the vertebrate ear are interspersed among supporting cells, forming a fine-grained pattern of alternating cell types. Analogies with Drosophila mechanosensory bristle development suggest that this pattern could be generated through lateral inhibition mediated by Notch signalling. In the zebrafish ear rudiment, homologues of Notch are widely expressed, while the Delta homologues deltaA, deltaB and deltaD, coding for Notch ligands, are expressed in small numbers of cells in regions where hair cells are soon to differentiate. This suggests that the delta-expressing cells are nascent hair cells, in agreement with findings for Delta1 in the chick. According to the lateral inhibition hypothesis, the nascent hair cells, by expressing Delta protein, would inhibit their neighbours from becoming hair cells, forcing them to be supporting cells instead. The zebrafish mind bomb mutant has abnormalities in the central nervous system, somites, and elsewhere, diagnostic of a failure of Delta-Notch signalling: in the CNS, it shows a neurogenic phenotype accompanied by misregulated delta gene expression. Similar misregulation of delta; genes is seen in the ear, along with misregulation of a Serrate homologue, serrateB, coding for an alternative Notch ligand. Most dramatically, the sensory patches in the mind bomb ear consist solely of hair cells, which are produced in great excess and prematurely; at 36 hours post fertilization, there are more than ten times as many as normal, while supporting cells are absent. A twofold increase is seen in the number of otic neurons also. The findings are strong evidence that lateral inhibition mediated by Delta-Notch signalling controls the pattern of sensory cell differentiation in the ear.

Ectodermal patterning in the avian embryo: epidermis versus neural plate

Development ◽  
1999 ◽  
Vol 126 (1) ◽  
pp. 63-73 ◽  
Author(s):  
E. Pera ◽  
S. Stein ◽  
M. Kessel
Keyword(s):  
Chick Embryo ◽  
Neural Crest ◽  
Plate Boundary ◽  
Homeobox Gene ◽  
Primitive Streak ◽  
Neural Plate ◽  
Avian Embryo ◽  
Neural Fate ◽  
Early Stages ◽  
Two Factors

Ectodermal patterning of the chick embryo begins in the uterus and continues during gastrulation, when cells with a neural fate become restricted to the neural plate around the primitive streak, and cells fated to become the epidermis to the periphery. The prospective epidermis at early stages is characterized by the expression of the homeobox gene DLX5, which remains an epidermal marker during gastrulation and neurulation. Later, some DLX5-expressing cells become internalized into the ventral forebrain and the neural crest at the hindbrain level. We studied the mechanism of ectodermal patterning by transplantation of Hensen's nodes and prechordal plates. The DLX5 marker indicates that not only a neural plate, but also a surrounding epidermis is induced in such operations. Similar effects can be obtained with neural plate grafts. These experiments demonstrate that the induction of a DLX5-positive epidermis is triggered by the midline, and the effect is transferred via the neural plate to the periphery. By repeated extirpations of the endoderm we suppressed the formation of an endoderm/mesoderm layer under the epiblast. This led to the generation of epidermis, and to the inhibition of neuroepithelium in the naked ectoderm. This suggests a signal necessary for neural, but inhibitory for epidermal development, normally coming from the lower layers. Finally, we demonstrate that BMP4, as well as BMP2, is capable of inducing epidermal fate by distorting the epidermis-neural plate boundary. This, however, does not happen independently within the neural plate or outside the normal DLX5 domain. In the area opaca, the co-transplantation of a BMP4 bead with a node graft leads to the induction of DLX5, thus indicating the cooperation of two factors. We conclude that ectodermal patterning is achieved by signalling both from the midline and from the periphery, within the upper but also from the lower layers.

scholarly journals Neural Induction, Neural Fate Stabilization, and Neural Stem Cells

2002 ◽  
Vol 2 ◽  
pp. 1147-1166 ◽  
Author(s):  
Sally A. Moody ◽  
Hyun-Soo Je
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Neural Stem Cells ◽  
Neural Development ◽  
Current Knowledge ◽  
Embryonic Stem ◽  
Neural Induction ◽  
Neural Plate ◽  
Natural Rate ◽  
Neural Fate

The promise of stem cell therapy is expected to greatly benefit the treatment of neurodegenerative diseases. An underlying biological reason for the progressive functional losses associated with these diseases is the extremely low natural rate of self-repair in the nervous system. Although the mature CNS harbors a limited number of self-renewing stem cells, these make a significant contribution to only a few areas of brain. Therefore, it is particularly important to understand how to manipulate embryonic stem cells and adult neural stem cells so their descendants can repopulate and functionally repair damaged brain regions. A large knowledge base has been gathered about the normal processes of neural development. The time has come for this information to be applied to the problems of obtaining sufficient, neurally committed stem cells for clinical use. In this article we review the process of neural induction, by which the embryonic ectodermal cells are directed to form the neural plate, and the process of neural�fate stabilization, by which neural plate cells expand in number and consolidate their neural fate. We will present the current knowledge of the transcription factors and signaling molecules that are known to be involved in these processes. We will discuss how these factors may be relevant to manipulating embryonic stem cells to express a neural fate and to produce large numbers of neurally committed, yet undifferentiated, stem cells for transplantation therapies.

scholarly journals Delta-Notch Signaling: The Long and The Short of a Neuron’s Influence on Progenitor Fates

2020 ◽  
Vol 8 (2) ◽  
pp. 8 ◽  
Author(s):  
Rachel Moore ◽  
Paula Alexandre
Keyword(s):  
Progenitor Cell ◽  
Radial Glia ◽  
Notch Signalling ◽  
Neural Progenitors ◽  
Cell Fates ◽  
Basal Surface ◽  
Neuroepithelial Cells ◽  
Mantle Layer ◽  
The Central Nervous System ◽  
Radial Glial

Maintenance of the neural progenitor pool during embryonic development is essential to promote growth of the central nervous system (CNS). The CNS is initially formed by tightly compacted proliferative neuroepithelial cells that later acquire radial glial characteristics and continue to divide at the ventricular (apical) and pial (basal) surface of the neuroepithelium to generate neurons. While neural progenitors such as neuroepithelial cells and apical radial glia form strong connections with their neighbours at the apical and basal surfaces of the neuroepithelium, neurons usually form the mantle layer at the basal surface. This review will discuss the existing evidence that supports a role for neurons, from early stages of differentiation, in promoting progenitor cell fates in the vertebrates CNS, maintaining tissue homeostasis and regulating spatiotemporal patterning of neuronal differentiation through Delta-Notch signalling.

scholarly journals Pairing your Sox: Identification of Sox11 partner proteins and interaction domains in the developing neural plate

2020 ◽  
Author(s):  
Kaela S. Singleton ◽  
Pablo Silva-Rodriguez ◽  
Elena M. Silva
Keyword(s):  
Protein Interactions ◽  
Neural Development ◽  
Specific Protein ◽  
Neural Plate ◽  
Neural Fate ◽  
Mouse Cortex ◽  
Interaction Domains ◽  
Species Specific ◽  
And Function ◽  
Partner Proteins

AbstractSox11, a member of the SoxC family of transcription factors, has distinct functions at different times in neural development. Studies in mouse, frog, chick and zebrafish show that Sox11 promotes neural fate, neural differentiation, and neuron maturation in the central nervous system. These diverse roles are controlled in part by spatial and temporal-specific protein interactions. However, the partner proteins and Sox11-interaction domains underlying these diverse functions are not well defined. Here, we identify partner proteins and the domains of Xenopus Sox11(xSox11) required for protein interaction and function during neurogenesis. Our data show that Sox11 co-localizes and interacts with Pou3f2 and Ngn2 in the anterior neural plate and in early neurons, respectively. We also demonstrate that xSox11 does not interact with Ngn1, a high affinity partner of Sox11 in the mouse cortex, suggesting that Sox11 has species-specific partner proteins. Additionally, we determined that the N-terminus including the HMG domain of xSox11 is necessary for interaction with Pou3f2 and Ngn2, and established a novel role for the N-terminal 46 amino acids in the establishment of placodal progenitors. This is the first identification of partner proteins for Xenopus Sox11 and of domains required for partner protein interactions and distinct roles in neurogenesis.

Retinoid receptors promote primary neurogenesis in Xenopus

Development ◽  
1997 ◽  
Vol 124 (2) ◽  
pp. 515-523 ◽  
Author(s):  
C.R. Sharpe ◽  
K. Goldstone
Keyword(s):  
Retinoic Acid ◽  
Nuclear Hormone Receptor ◽  
Retinoic Acid Receptors ◽  
Primary Neurons ◽  
Retinoid X Receptors ◽  
Over Expression ◽  
Retinoid Receptors ◽  
X Receptors ◽  
Synthetic Mrna ◽  
Primary Neurogenesis

Retinoid receptors, which are members of the nuclear hormone receptor superfamily, act as ligand-dependent transcription factors. They mediate the effects of retinoic acid primarily as heterodimers of retinoic acid receptors (RARs) and retinoid X receptors (RXRs). To analyse their function, xRXR beta synthetic mRNA was injected into Xenopus embryos in combination with normal and mutated xRAR alpha transcripts. Two informative phenotypes are reported here. Firstly, over-expression of xRXR beta with xRAR alpha results in the formation of ectopic primary neurons. Secondly, blocking retinoid signalling with a mutated xRAR alpha results in a lack of primary neurons. These two phenotypes, from contra-acting manipulations, indicate a role for retinoid signalling during neurogenesis.

her4, a zebrafish homologue of the Drosophila neurogenic gene E(spl), is a target of NOTCH signalling

Development ◽  
1999 ◽  
Vol 126 (9) ◽  
pp. 1811-1821 ◽  
Author(s):  
C. Takke ◽  
P. Dornseifer ◽  
E. v Weizsacker ◽  
J.A. Campos-Ortega
Keyword(s):  
Feedback Loop ◽  
Bhlh Protein ◽  
Primary Neurons ◽  
Amino Terminal ◽  
Early Neurogenesis ◽  
Regulatory Feedback Loop ◽  
Carboxy Terminal ◽  
Her4 Expression ◽  
Primary Neurogenesis ◽  
Developing Nervous System

her4 encodes a zebrafish bHLH protein of the hairy-E(spl) family. The gene is transcribed in a complex pattern in the developing nervous system and in the hypoblast. During early neurogenesis, her4 expression domains include the regions of the neural plate from which primary neurons arise, suggesting that the gene is involved in directing their development. Indeed, misexpression of specific her4 variants leads to a reduction in the number of primary neurons formed. The amino-terminal region of her4, including the basic domain, and the region between the putative helix IV and the carboxy-terminal tetrapeptide wrpw are essential for this effect, since her4 variants lacking either of these regions are non-functional. However, the carboxy-terminal wrpw itself is dispensable. We have examined the interrelationships between deltaD, deltaA, notch1, her4 and neurogenin1 by means of RNA injections. her4 is involved in a regulatory feedback loop which modulates the activity of the proneural gene neurogenin, and as a consequence, of deltaA and deltaD. Activation of notch1 leads to strong activation of her4, to suppression of neurogenin transcription and, ultimately, to a reduction in the number of primary neurons. These results suggest that her4 acts as a target of notch-mediated signals that regulate primary neurogenesis.

Sign in / Sign up

Export Citation Format

Share Document