Characterization of Xenopus Phox2a and Phox2b defines expression domains within the embryonic nervous system and early heart field

doi:10.1016/j.modgep.2004.01.012

Gene Expression Patterns

Volume 4, Issue 5, September 2004, Pages 601-607

https://doi.org/10.1016/j.modgep.2004.01.012 Get rights and content

Abstract

The closely related homeodomain containing genes, Phox2a and Phox2b, are essential for neuronal specification and differentiation within discrete subsets of neurons during vertebrate embryogenesis. We have isolated Xenopus Phox2 homologs, termed Xphox2a and Xphox2b, and characterized their expression during early development. In addition, we have characterized a Phox2a splice variant, termed Xphox2a.2, which lacks homeo- and C-terminal protein coding domains. Xphox2a, Xphox2a.2 and Xphox2b transcripts are expressed in dynamic temporal and regional patterns during nervous system development. The expression of Xphox2a and Xphox2b is only partially overlapping and includes cranial motor and interneuron populations as well as peripheral sympathetic and cranial ganglion neurons, sites linked to Phox2 expression in other species. In addition, we have identified an early domain of Xphox2a and subsequent Xphox2b expression in ventral regions of the embryo, within the developing heart field. XPhox2 expression within this domain is preceded by the gastrula-stage expression of the proneural basic helix–loop–helix transcription factor, Xash1, pointing to a new region of action for this group transcription factors during vertebrate development.

Section snippets

Results and discussion

The closely related homeodomain containing genes, Phox2a and Phox2b, are expressed in restricted subsets of central and peripheral progenitors and neurons in species ranging from fish to humans (Amiel et al., 2003, Guo et al., 1999, Pattyn et al., 1997, Tiveron et al., 1996). Both gain and loss of function assays suggest that Phox2a and Phox2b homeodomain containing molecules are important regulators of vertebrate neuronal specification and differentiation (for review, Brunet and Pattyn, 2002).

Characterization of Xphox2a, Xphox2a.2 and Xphox2b

The Xphox2a.2 cDNA was identified in a screen of the Xenopus TIGR database (The Institute for Genome Research; http://www.tigr.org/tdb/tgi/) using murine Phox2a sequences. This clone was obtained via the I.M.A.G.E. Consortium (ID# 3438199; http://image.llnl.gov). The Xphox2a cDNA was isolated in a screen of a Stage 27 head library (Hemmati-Brivanlou et al., 1990) using the Xphox2a.2 cDNA as a probe. The Xphox2b clone was identified in a functional expression screen using an early gastrula stage

Acknowledgements

This work was supported by NIH grant RO1 HD32968 (K.Z.) and RO1 HD32105 (A.H.B). K.Z. also gratefully acknowledges the generous support and encouragement of Dr Mary E. Hatten.

References (31)

J.F Brunet et al.
Phox2 genes-from patterning to connectivity
Curr. Opin. Genet. Dev.
(2002)
S Guo et al.
Development of noradrenergic neurons in the zebrafish hindbrain requires BMP, FGF8, and the homeodomain protein soulless/Phox2a
Neuron
(1999)
R.M Harland
In situ hybridization: an improved whole mount method for Xenopus embryos
Methods Cell Biol.
(1991)
L Lo et al.
Specification of neurotransmitter identity by Phox2 proteins in neural crest stem cells
Neuron
(1999)
X Morin et al.
Defects in sensory and autonomic ganglia and absence of locus coeruleus in mice deficient for the homeobox gene Phox2a
Neuron
(1997)
A Pattyn et al.
Specification of the central noradrenergic phenotype by the homeobox gene Phox2b
Mol. Cell. Neurosci.
(2000)
M.C Tiveron et al.
Role of Phox2b and Mash1 in the generation of the vestibular efferent nucleus
Dev. Biol.
(2003)
K.F Tonissen et al.
XNkx-2.5, a Xenopus gene related to Nkx-2.5 and tinman: evidence for a conserved role in cardiac development
Dev. Biol.
(1994)
J Amiel et al.
Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome
Nat. Genet.
(2003)
S Angelo et al.
Conservation of sequence and expression of Xenopus and zebrafish dHAND during cardiac branchial arch and lateral mesoderm development
Mech. Dev.
(2000)

J.C Baker et al.

A novel mesoderm inducer, Madr2, functions in the activin signal transduction pathway

Genes Dev.

(1996)

V Dubreuil et al.

The Phox2b transcription factor coordinately regulates neuronal cell cycle exit and identity

Development

(2000)

Ferreiro, B., Skoglund, P., Bailey, A., Dorsky, R., Harris, W.A., 1993. XASH1, a Xenopus homolog of achaete-scute: a...

B Ferreiro et al.

XASH genes promote neurogenesis in Xenopus embryos

Development

(1994)

A Gershon et al.

The homeodomain-containing gene Xdbx inhibits neuronal differentiation in the developing embryo

Development

(2000)

Cited by (13)

Xenopus, an emerging model for studying pathologies of the neural crest
2021, Current Topics in Developmental Biology
Citation Excerpt :
For instance, the expression of pmp22, the gene encoding a myelin protein causing defective Schwann myelin protein function in the Charcot-Marie-Tooth syndrome, is controlled by Pax3 and Zic1 in the frog NC-GRN during early organogenesis (Bae et al., 2014; Tae et al., 2015). The expression of other genes causing altered differentiation of glial cells, such as in the Congenital Central Hypoventilation syndrome (altered sympathetic glia) was described in frog embryos, but not with a focus on glial differentiation (phox2a/b, Talikka, Stefani, Brivanlou, & Zimmerman, 2004; gdnf, Kyuno & Jones, 2007; ret, Carroll, Wallingford, Seufert, & Vize, 1999; edn3/ednr, Square, Jandzik, Cattell, Hansen, & Medeiros, 2016). This means that some molecular tools have been developed and could be directly used in NCP studies.
Neural crest cells are a multipotent embryonic stem cell population that emerges from the lateral border of the neural plate after an epithelium-to-mesenchyme transition. These cells then migrate extensively in the embryo and generate a large variety of differentiated cell types and tissues. Alterations in almost any of the processes involved in neural crest development can cause severe congenital defects in humans. Moreover, the malignant transformation of one of the many neural crest derivatives, during childhood or in adults, can cause the development of aggressive tumors prone to metastasis such as melanoma and neuroblastoma. Collectively these diseases are called neurocristopathies. Here we review how a variety of approaches implemented using the amphibian Xenopus as an experimental model have shed light on the molecular basis of numerous neurocristopathies, and how this versatile yet underused vertebrate animal model could help accelerate discoveries in the field. Using the current framework of the neural crest gene regulatory network, we review the pathologies linked to defects at each step of neural crest formation and highlight studies that have used the Xenopus model to decipher the cellular and molecular aspects of neurocristopathies.
Induction and specification of cranial placodes
2006, Developmental Biology
Cranial placodes are specialized regions of the ectoderm, which give rise to various sensory ganglia and contribute to the pituitary gland and sensory organs of the vertebrate head. They include the adenohypophyseal, olfactory, lens, trigeminal, and profundal placodes, a series of epibranchial placodes, an otic placode, and a series of lateral line placodes. After a long period of neglect, recent years have seen a resurgence of interest in placode induction and specification. There is increasing evidence that all placodes despite their different developmental fates originate from a common panplacodal primordium around the neural plate. This common primordium is defined by the expression of transcription factors of the Six1/2, Six4/5, and Eya families, which later continue to be expressed in all placodes and appear to promote generic placodal properties such as proliferation, the capacity for morphogenetic movements, and neuronal differentiation. A large number of other transcription factors are expressed in subdomains of the panplacodal primordium and appear to contribute to the specification of particular subsets of placodes. This review first provides a brief overview of different cranial placodes and then synthesizes evidence for the common origin of all placodes from a panplacodal primordium. The role of various transcription factors for the development of the different placodes is addressed next, and it is discussed how individual placodes may be specified and compartmentalized within the panplacodal primordium. Finally, tissues and signals involved in placode induction are summarized with a special focus on induction of the panplacodal primordium itself (generic placode induction) and its relation to neural induction and neural crest induction. Integrating current data, new models of generic placode induction and of combinatorial placode specification are presented.
The crucial role of model systems in understanding the complexity of cell signaling in human neurocristopathies
2022, WIREs Mechanisms of Disease
Evolution of the endothelin pathway drove neural crest cell diversification
2020, Nature
Whole-organism cellular gene-expression atlas reveals conserved cell types in the ventral nerve cord of Platynereis dumerilii
2017, Proceedings of the National Academy of Sciences of the United States of America
Ascl1 phospho-status regulates neuronal differentiation in a Xenopus developmental model of neuroblastoma
2015, DMM Disease Models and Mechanisms

View all citing articles on Scopus

View full text

Characterization of Xenopus Phox2a and Phox2b defines expression domains within the embryonic nervous system and early heart field

Abstract

Section snippets

Results and discussion

Characterization of Xphox2a, Xphox2a.2 and Xphox2b

Acknowledgements

Curr. Opin. Genet. Dev.

Neuron

Methods Cell Biol.

Neuron

Neuron

Mol. Cell. Neurosci.

Dev. Biol.

Dev. Biol.

Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome

Nat. Genet.

Conservation of sequence and expression of Xenopus and zebrafish dHAND during cardiac branchial arch and lateral mesoderm development

Mech. Dev.

A novel mesoderm inducer, Madr2, functions in the activin signal transduction pathway

Genes Dev.

The Phox2b transcription factor coordinately regulates neuronal cell cycle exit and identity

Development

XASH genes promote neurogenesis in Xenopus embryos

Development

The homeodomain-containing gene Xdbx inhibits neuronal differentiation in the developing embryo

Development