Vertebrate floor-plate specification: variations on common themes

doi:10.1016/j.tig.2004.01.002

Trends in Genetics

Volume 20, Issue 3, March 2004, Pages 155-162

https://doi.org/10.1016/j.tig.2004.01.002 Get rights and content

Abstract

Situated at the ventral-most part of the vertebrate neural tube, the floor plate (FP) is an important signalling centre that controls the regional differentiation of neurons in the nervous system. It secretes guidance molecules that direct ventrally navigating axons crucial for the correct wiring of neuronal circuits. Although the function of the FP is well-conserved from fish to humans, discrepancies exists with respect to both the signalling system involved in FP induction, and the origin of the FP in various vertebrate species. Recent findings from the embryos of zebrafish, chicken and mouse provide insights that reconcile previous results and suggest common themes in vertebrate FP specification.

Section snippets

Genetics of FP development in zebrafish

For most of its length, the zebrafish FP comprises a three-cell-wide row at the ventral-most aspect of the neural tube. It can be subdivided into the one-cell-wide medial FP (mFP) and the lateral FP (lFP) 15, 16, which differ in gene expression (Figure 2) and mechanism of development (Figure 3). The two sub-structures of the FP appear to develop asynchronously because expression of lFP markers is delayed with respect to differentiation of the mFP [15]. This subdivision and marker gene

The role of Hedgehog and Cyc signals in zebrafish FP development

Whereas Shh is necessary for specification of the entire FP in mouse, only the lFP in zebrafish appears to require Shh signals. The medial part of the FP is instead dependent on the Nodal-related signal, Cyc. Given the functions of Nodals in mesoderm formation in mouse and zebrafish, it was argued that Cyc is required for production of the FP-inducing signal [9]. As there are several, highly related hedgehog genes in zebrafish [26] that are expressed in an overlapping pattern, this fostered

The cis-regulatory paradox

The zebrafish shh gene is expressed in axial mesoderm, mFP, zona limitans intrathalamica, and hypothalamus of the ventral forebrain [26] (Figure 4a). This pattern of expression is highly similar to that of mouse shh [26]. Functional mapping of the cis-regulatory structure of the two orthologous genes shows similarities and differences, with both genes using multiple enhancers to control expression 45, 46. In the zebrafish shh gene, four regulatory regions (ar-A, ar-B, ar-C and ar-D) were mapped

The chicken controversy

The FP-induction model derived from grafting experiments in chicken embryos suggests an important role of the notochord and prechordal plate as FP-inducing tissues (Figure 5). Placing notochord or prechordal plate tissue in close juxtaposition to naive neural tissue leads to the differentiation of FP, a process that can also be mimicked by recombinant Shh [10]. However, this model does not correlate with data from zebrafish and was also questioned by results from cell-fate mapping experiments

FP specification in lower and higher vertebrates: not so different after all?

Interestingly, in chick, the prechordal plate was found to be a significantly more potent FP inducer than the notochord, when compared for their respective FP-inducing activity in grafting experiments [59]. This suggests that the prechordal plate either expresses higher levels of Shh or uses additional factors that specify FP character. When isolated before contact with prechordal plate, area-a cells failed to express Shh and Foxa2. Expression of these markers can be induced when naive area-a

Concluding remarks

Development of the FP is based on the intricate interplay of several signalling pathways. Moreover, distinct mechanisms of FP specification operate along the anteroposterior axis. While the posterior FP appears to use an induction and/or allocation mechanism, the anterior FP appears to be specified by the classical induction model. The FP functions as a neural-tube organizer throughout the vertebrate group, and many of the mechanistic features of FP development are also shared. However, there

Acknowledgements

We thank Dominique Biellmann and Sandra Metz for artwork, and Marie-Aimée Teillet for discussions. We apologize to those authors whose work could not be cited owing to space limitations. C.S.L. is a scholar of ASTAR, Singapore. This work was supported by CNRS/INSERM/ULP/HUS, AFM, ARC, Volkswagen Stiftung and AICR.

Glossary

Interneuron:: these connect sensory, motor and motivated systems in the central nervous system. They serve as relays that transmit and modify neural information. Commissural interneurons have trajectories that cross the midline, connecting the left and right halves of the nervous system.
Amniotes:: the presence of an amnion (a fluid-filled sac) surrounding the embryos of reptiles, birds and mammals, defines these vertebrates as amniotes. Fish and amphibians are referred to as anamniotes because

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Commissural axon navigation in the spinal cord: A repertoire of repulsive forces is in command
2019, Seminars in Cell and Developmental Biology
The navigation of commissural axons in the developing spinal cord has attracted multiple studies over the years. Many important concepts emerged from these studies which have enlighten the general mechanisms of axon guidance. The navigation of commissural axons is regulated by a series of cellular territories which provides the diverse guidance information necessary to ensure the successive steps of their pathfinding towards, across, and away from the ventral midline. In this review, we discuss how repulsive forces, by propelling, channelling, and confining commissural axon navigation, bring key contributions to the formation of this neuronal projection.
A novel role for FOXA2 and SHH in organizing midbrain signaling centers
2012, Developmental Biology
Citation Excerpt :
These results suggest that HH is required for the specification and/or maintenance of all midbrain signaling centers, including the FP, RP and the MHB. Our results suggest that SHH is both necessary and sufficient for LFP induction, but it is only necessary, and not sufficient for inducing the MFP program (Odenthal et al., 2000; Strahle et al., 2004). By contrast, FOXA2 is necessary and sufficient to specify the entire FP and does so in a HH-dependent and independent manner (Fig. 8).
The floor plate (FP) is a midline signaling center, known to direct ventral cell fates and axon guidance in the neural tube. The recent identification of midbrain FP as a source of dopaminergic neurons has renewed interest in its specification and organization, which remain poorly understood. In this study, we have examined the chick midbrain and spinal FP and show that both can be partitioned into medial (MFP) and lateral (LFP) subdivisions. Although Hedgehog (HH) signaling is necessary and sufficient for LFP specification, it is not sufficient for MFP induction. By contrast, the transcription factor FOXA2 can execute the full midbrain and spinal cord FP program via HH-independent and dependent mechanisms. Interestingly, although HH-independent FOXA2 activity is necessary and sufficient for inducing MFP-specific gene expression (e.g., LMX1B, BMP7), it cannot confer ventral identity to midline cells without also turning on Sonic hedgehog (SHH).
We also note that the signaling centers of the midbrain, the FP, roof plate (RP) and the midbrain–hindbrain boundary (MHB) are physically contiguous, with each expressing LMX1B and BMP7. Possibly as a result, SHH or FOXA2 misexpression can transform the MHB into FP and also suppress RP induction. Conversely, HH or FOXA2 knockdown expands the endogenous RP and transforms the MFP into a RP and/or MHB fate. Finally, combined HH blockade and FOXA2 misexpression in ventral midbrain induces LMX1B expression, which triggers the specification of the RP, rather than the MFP. Thus we identify HH-independent and dependent roles for FOXA2 in specifying the FP. In addition, we elucidate for the first time, a novel role for SHH in determining whether a midbrain signaling center will become the FP, MHB or RP.
A revised model of Xenopus dorsal midline development: Differential and separable requirements for Notch and Shh signaling
2011, Developmental Biology
The development of the vertebrate dorsal midline (floor plate, notochord, and hypochord) has been an area of classical research and debate. Previous studies in vertebrates have led to contrasting models for the roles of Shh and Notch signaling in specification of the floor plate, by late inductive or early allocation mechanisms, respectively. Here, we show that Notch signaling plays an integral role in cell fate decisions in the dorsal midline of Xenopus laevis, similar to that observed in zebrafish and chick. Notch signaling promotes floor plate and hypochord fates over notochord, but has variable effects on Shh expression in the midline. In contrast to previous reports in frog, we find that Shh signaling is not required for floor plate vs. notochord decisions and plays a minor role in floor plate specification, where it acts in parallel to Notch signaling. As in zebrafish, Shh signaling is required for specification of the lateral floor plate in the frog. We also find that the medial floor plate in Xenopus comprises two distinct populations of cells, each dependent upon different signals for its specification. Using expression analysis of several midline markers, and dissection of functional relationships, we propose a revised allocation mechanism of dorsal midline specification in Xenopus. Our model is distinct from those proposed to date, and may serve as a guide for future studies in frog and other vertebrate organisms.
Foxa2 regulates the expression of Nato3 in the floor plate by a novel evolutionarily conserved promoter
2011, Molecular and Cellular Neuroscience
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Thus, it was reasonable to assume that the regulatory mechanisms governing Nato3 transcription are also evolutionarily conserved, and may involve a set of orthologous transcription factors. Indeed, several lines of evidence suggest that components of regulatory circuits controlling expression and function in the FP are conserved between mouse and chick, and in some aspects also in fish (Briscoe and Therond, 2005; Strahle et al., 2004). Our approach towards the identification of regulators of Nato3 in the FP is based on the growing list of studies suggesting that evolutionarily conserved non-coding sequences often correspond with tissue specific regulatory elements, such as enhancers (Fortini and Rubin, 1990; Gomez-Skarmeta et al., 2006; Pennacchio et al., 2006; Woolfe et al., 2005).
The development of the neural tube into a complex central nervous system involves morphological, cellular and molecular changes, all of which are tightly regulated. The floor plate (FP) is a critical organizing center located at the ventral-most midline of the neural tube. FP cells regulate dorsoventral patterning, differentiation and axon guidance by secreting morphogens. Here we show that the bHLH transcription factor Nato3 (Ferd3l) is specifically expressed in the spinal FP of chick and mouse embryos. Using in ovo electroporation to understand the regulation of the FP-specific expression of Nato3, we have identified an evolutionarily conserved 204 bp genomic region, which is necessary and sufficient to drive expression to the chick FP. This promoter contains two Foxa2-binding sites, which are highly conserved among distant phyla. The two sites can bind Foxa2 in vitro, and are necessary for the expression in the FP in vivo. Gain and loss of Foxa2 function in vivo further emphasize its role in Nato3 promoter activity. Thus, our data suggest that Nato3 is a direct target of Foxa2, a transcription activator and effector of Sonic hedgehog, the hallmark regulator of FP induction and spinal cord development. The identification of the FP-specific promoter is an important step towards a better understanding of the molecular mechanisms through which Nato3 transcription is regulated and for uncovering its function during nervous system development. Moreover, the promoter provides us with a powerful tool for conditional genetic manipulations in the FP.
Neurogenesis
2010, Methods in Cell Biology
Citation Excerpt :
These signals not only induce the neurogenic cascade (i.e., Shh induces neurog1 expression Blader et al., 1997) but also specify neuronal identity and the size of the neuronal clusters, for example, the role of Wnt in the diencephalic dopaminergic population (Lee et al., 2006; Russek-Blum et al., 2008). Such signaling centers include the floor plate which secretes Shh and Twhh (Ribes et al., 2010; Strahle et al., 2004), the roof plate with Wnt signaling activity (Amoyel et al., 2005), the interrhombomeric boundary cells in the hindbrain conveying Wnt1 signaling activity and inducing deltaA expression in rhombomeres (Amoyel et al., 2005), rhombomere 4 conveying FGF3 and FGF8 signaling activity (Maves et al., 2002), the zona limitans intrathalamica (ZLI), with Shh and Twhh (Scholpp et al., 2006, 2009), and the isthmic organizer at the mid-hindbrain boundary (Raible and Brand, 2004; Wurst and Bally-Cuif, 2001) with FGF and Wnt signaling activity orchestrating the growth of the midbrain and rhombomere 1. Downstream of these signaling pathways, transcription factor combinations are activated in a temporal and region-specific manner and define specific differentiation programs, thereby producing a variety of neuronal phenotypes.
For more than a decade, the zebrafish has proven to be an excellent model organism to investigate the mechanisms of neurogenesis during development. The often cited advantages, namely external development, genetic, and optical accessibility, have permitted direct examination and experimental manipulations of neurogenesis during development. Recent studies have begun to investigate adult neurogenesis, taking advantage of its widespread occurrence in the mature zebrafish brain to investigate the mechanisms underlying neural stem cell maintenance and recruitment. Here we provide a comprehensive overview of the tools and techniques available to study neurogenesis in zebrafish both during development and in adulthood. As useful resources, we provide tables of available molecular markers, transgenic, and mutant lines. We further provide optimized protocols for studying neurogenesis in the adult zebrafish brain, including in situ hybridization, immunohistochemistry, in vivo lipofection and electroporation methods to deliver expression constructs, administration of bromodeoxyuridine (BrdU), and finally slice cultures. These currently available tools have put zebrafish on par with other model organisms used to investigate neurogenesis.
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Trends in Genetics

Vertebrate floor-plate specification: variations on common themes

Abstract

Section snippets

Genetics of FP development in zebrafish

The role of Hedgehog and Cyc signals in zebrafish FP development

The cis-regulatory paradox

The chicken controversy

FP specification in lower and higher vertebrates: not so different after all?

Concluding remarks

Acknowledgements

Glossary

Glossary

Neuron

Cell

Cell

Curr. Opin. Neurobiol.

Cell

Curr. Opin. Neurobiol.

Dev. Biol.

Curr. Biol.

Curr. Biol.

Cell

Mol. Cell

Dev. Biol.

Dev. Biol.

Dev. Biol.

Cell

Cell

Mech. Dev.

Cell

Curr. Biol.

Dev. Biol.

Cell

Cell

Dev. Cell

The developmental significance of the floor plate of the brain and spinal cord

J. Comp. Neurol.

The role of the floor plate in axon guidance

Annu. Rev. Neurosci.

Diversity and pattern in the developing spinal cord

Science

Zebrafish neural induction and patterning

Dev. Dyn.

Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function

Nature

The when and where of floor plate induction

Science

Requirement of 19K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explants

Nature

A spinal cord fate map in the avian embryo: while regressing Hensen's node lays down the notochord and floor plate thus joining the spinal cord lateral walls

Development

Expression of axial and sonic hedgehog in wildtype and midline defective zebrafish embryos

Int. J. Dev. Biol.

Requirement for the homeobox gene floating head in zebrafish development

Nature

Cell-autonomous shift from axial to paraxial mesodermal development in zebrafish floating head mutants

Development

Zebrafish organizer development and germ-layer formation require nodal-related signals

Nature

The zebrafish T-box genes no tail and spadetail are required for development of trunk and tail mesoderm and medial floor plate

Development

The cyclops mutation blocks specification of the floor plate of the zebrafish central nervous system

Nature