Homologs of genes expressed in Caenorhabditis elegans GABAergic neurons are also found in the developing mouse forebrain

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Abstract

Background

In an effort to identify genes that specify the mammalian forebrain, we used a comparative approach to identify mouse homologs of transcription factors expressed in developing Caenorhabditis elegans GABAergic neurons. A cell-specific microarray profiling study revealed a set of transcription factors that are highly expressed in embryonic C. elegans GABAergic neurons.

Results

Bioinformatic analyses identified mouse protein homologs of these selected transcripts and their expression pattern was mapped in the mouse embryonic forebrain by in situ hybridization. A review of human homologs indicates several of these genes are potential candidates in neurodevelopmental disorders.

Conclusions

Our comparative approach has revealed several novel candidates that may serve as future targets for studies of mammalian forebrain development.

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Most cited references 44

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Interneurons of the neocortical inhibitory system.

Henry Markram, Maria Toledo-Rodriguez, Yun Wang … (2004)

Mammals adapt to a rapidly changing world because of the sophisticated cognitive functions that are supported by the neocortex. The neocortex, which forms almost 80% of the human brain, seems to have arisen from repeated duplication of a stereotypical microcircuit template with subtle specializations for different brain regions and species. The quest to unravel the blueprint of this template started more than a century ago and has revealed an immensely intricate design. The largest obstacle is the daunting variety of inhibitory interneurons that are found in the circuit. This review focuses on the organizing principles that govern the diversity of inhibitory interneurons and their circuits.

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

Jeanne Amiel, Béatrice Laudier, Tania Attie-Bitach … (2003)

Congenital central hypoventilation syndrome (CCHS or Ondine's curse; OMIM 209880) is a life-threatening disorder involving an impaired ventilatory response to hypercarbia and hypoxemia. This core phenotype is associated with lower-penetrance anomalies of the autonomic nervous system (ANS) including Hirschsprung disease and tumors of neural-crest derivatives such as ganglioneuromas and neuroblastomas. In mice, the development of ANS reflex circuits is dependent on the paired-like homeobox gene Phox2b. Thus, we regarded its human ortholog, PHOX2B, as a candidate gene in CCHS. We found heterozygous de novo mutations in PHOX2B in 18 of 29 individuals with CCHS. Most mutations consisted of 5-9 alanine expansions within a 20-residue polyalanine tract probably resulting from non-homologous recombination. We show that PHOX2B is expressed in both the central and the peripheral ANS during human embryonic development. Our data support an essential role of PHOX2B in the normal patterning of the autonomous ventilation system and, more generally, of the ANS in humans.

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The temporal and spatial origins of cortical interneurons predict their physiological subtype.

Simon J B Butt, Marc Fuccillo, Susana Vaz Nery … (2005)

Interneurons of the cerebral cortex represent a heterogeneous population of cells with important roles in network function. At present, little is known about how these neurons are specified in the developing telencephalon. To explore whether this diversity is established in the early progenitor populations, we conducted in utero fate-mapping of the mouse medial and caudal ganglionic eminences (MGE and CGE, respectively), from which most cortical interneurons arise. Mature interneuron subtypes were assessed by electrophysiological and immunological analysis, as well as by morphological reconstruction. At E13.5, the MGE gives rise to fast-spiking (FS) interneurons, whereas the CGE generates predominantly regular-spiking interneurons (RSNP). Later at E15.5, the CGE produces RSNP classes distinct from those generated from the E13.5 CGE. Thus, we provide evidence that the spatial and temporal origin of interneuron precursors in the developing telencephalic eminences predicts the intrinsic physiological properties of mature interneurons.

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Author and article information

Journal

Journal ID (nlm-ta): Neural Dev

Title: Neural Development

Publisher: BioMed Central

ISSN (Electronic): 1749-8104

Publication date Collection: 2010

Publication date (Electronic): 1 December 2010

Volume: 5

Page: 32

Affiliations

[1 ]Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA

[2 ]Vanderbilt Kennedy Center, Vanderbilt University, Nashville, TN 37232, USA

[3 ]Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA

[4 ]Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232-8240, USA

[5 ]Program in Neuroscience, Vanderbilt University, Nashville, TN 37232-8240, USA

[6 ]Siskin Hospital for Physical Rehabilitation, One Siskin Plaza, Chattanooga, TN 37403, USA

[7 ]St Jude Children's Research Hospital, Memphis, TN 38105, USA

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Publisher ID: 1749-8104-5-32

DOI: 10.1186/1749-8104-5-32

PMC ID: 3006369

PubMed ID: 21122108

SO-VID: 3144cb16-483c-4a35-b417-dfad8d9ebbc9

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<url>http://creativecommons.org/licenses/by/2.0</url>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Homologs of genes expressed in Caenorhabditis elegans GABAergic neurons are also found in the developing mouse forebrain

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Abstract

Background

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Conclusions

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Most cited references 44

Interneurons of the neocortical inhibitory system.

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

The temporal and spatial origins of cortical interneurons predict their physiological subtype.

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