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Barx2, a new homeobox gene of the Bar class, is expressed in neural and craniofacial structures during development.

ABSTRACT: Homeobox genes are regulators of place-dependent morphogenesis and play important roles in controlling the expression patterns of cell adhesion molecules (CAMs). To identify proteins that bind to a regulatory element common to the genes for two neural CAMs, Ng-CAM and L1, we screened a mouse cDNA expression library with a concatamer of the sequence CCATTAGPyGA and found a new homeobox gene, which we have called Barx2. The homeodomain encoded by Barx2 is 87% identical to that of Barx1, and both genes are related to genes at the Bar locus of Drosophila melanogaster. Barx1 and Barx2 also encode an identical stretch of 17 residues downstream of the homeobox; otherwise, they share no appreciable homology. In vitro, Barx2 stimulated activity of an L1 promoter construct containing the CCATTAGPyGA motif but repressed activity when this sequence was deleted. Localization studies showed that expression of Barx1 and Barx2 overlap in the nervous system, particularly in the telencephalon, spinal cord, and dorsal root ganglia. Barx2 was also prominently expressed in the floor plate and in Rathke's pouch. During craniofacial development, Barx1 and Barx2 showed complementary patterns of expression: whereas Barx1 appeared in the mesenchyme of the mandibular and maxillary processes, Barx2 was observed in the ectodermal lining of these tissues. Intense expression of Barx2 was observed in small groups of cells undergoing tissue remodeling, such as ectodermal cells within indentations surrounding the eye and maxillo-nasal groove and in the first branchial pouch, lung buds, precartilagenous condensations, and mesenchyme of the limb. The localization data, combined with Barx2's dual function as activator and repressor, suggest that Barx2 may differentially control the expression of L1 and other target genes during embryonic development.

SUBMITTER: Jones FS

PROVIDER: S-EPMC20140 | biostudies-literature | 1997 Mar

REPOSITORIES: biostudies-literature

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Barx2, a new homeobox gene of the Bar class, is expressed in neural and craniofacial structures during development.

Jones F S FS Kioussi C C Copertino D W DW Kallunki P P Holst B D BD Edelman G M GM

Proceedings of the National Academy of Sciences of the United States of America 19970301 6

Homeobox genes are regulators of place-dependent morphogenesis and play important roles in controlling the expression patterns of cell adhesion molecules (CAMs). To identify proteins that bind to a regulatory element common to the genes for two neural CAMs, Ng-CAM and L1, we screened a mouse cDNA expression library with a concatamer of the sequence CCATTAGPyGA and found a new homeobox gene, which we have called Barx2. The homeodomain encoded by Barx2 is 87% identical to that of Barx1, and both g ...[more]

PMID: 9122247

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Project description:Holoprosencephaly (HPE), the most common malformation of the human forebrain, is associated with defects of the craniofacial skeleton. ZIC2, a zinc-finger transcription factor, is strongly linked to HPE and to a characteristic set of dysmorphic facial features in humans. We have previously identified important functions for zebrafish Zic2 in the developing forebrain. Here, we demonstrate that ZIC2 orthologs zic2a and zic2b also regulate the forming zebrafish craniofacial skeleton, including the jaw and neurocranial cartilages, and use the zebrafish to study Zic2-regulated processes that may contribute to the complex etiology of HPE. Using temporally controlled Zic2a overexpression, we show that the developing craniofacial cartilages are sensitive to Zic2 elevation prior to 24hpf. This window of sensitivity overlaps the critical expansion and migration of the neural crest (NC) cells, which migrate from the developing neural tube to populate vertebrate craniofacial structures. We demonstrate that zic2b influences the induction of NC at the neural plate border, while both zic2a and zic2b regulate NC migratory onset and strongly contribute to chromatophore development. Both Zic2 depletion and early ectopic Zic2 expression cause moderate, incompletely penetrant mispatterning of the NC-derived jaw precursors at 24hpf, yet by 2dpf these changes in Zic2 expression result in profoundly mispatterned chondrogenic condensations. We attribute this discrepancy to an additional role for Zic2a and Zic2b in patterning the forebrain primordium, an important signaling source during craniofacial development. This hypothesis is supported by evidence that transplanted Zic2-deficient cells can contribute to craniofacial cartilages in a wild-type background. Collectively, these data suggest that zebrafish Zic2 plays a dual role during craniofacial development, contributing to two disparate aspects of craniofacial morphogenesis: (1) neural crest induction and migration, and (2) early patterning of tissues adjacent to craniofacial chondrogenic condensations.

Dataset Information

Barx2, a new homeobox gene of the Bar class, is expressed in neural and craniofacial structures during development.

Publications

Barx2, a new homeobox gene of the Bar class, is expressed in neural and craniofacial structures during development.

Similar Datasets

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