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issn:1567-133
1.  Gene expression patterns in primary neuronal clusters of the Drosophila embryonic brain 
Gene expression patterns : GEP  2007;7(5):584-595.
The brain of Drosophila is formed by approximately 100 lineages, each lineage being derived from a stem cell-like neuroblast that segregates from the procephalic neurectoderm of the early embryo. A neuroblast map has been established in great detail for the early embryo, and a suite of molecular markers has been defined for all neuroblasts included in this map (Urbach and Technau, 2003a). However, the expression of these markers was not followed into later embryonic or larval stages, mainly due to the fact that anatomical landmarks to which expression patterns could be related had not been defined. Such markers, in the form of stereotyped clusters of neurons whose axons project along cohesive bundles (“primary axon bundles” or “PABs”) are now available (Younossi-Hartenstein et al., 2006). In the present study we have mapped the expression of molecular markers in relationship to primary neuronal clusters and their PABs. The markers we analyzed include many of the genes involved in patterning of the brain along the anteroposterior axis (cephalic gap genes, segment polarity genes) and dorso-ventral axis (columnar patterning genes), as well as genes expressed in the dorsal protocerebrum and visual system (early eye genes). Our analysis represents an important step along the way to identify neuronal lineages of the mature brain with genes expressed in the early embryo in discrete neuroblasts. Furthermore, the analysis helped us to reconstruct the morphogenetic movements that transform the two-dimensional neuroblast layer of the early embryo into the three-dimensional larval brain and provides the basis for deeper understanding of how the embryonic brain develops.
doi:10.1016/j.modgep.2007.01.004
PMCID: PMC3928073  PMID: 17300994
Drosophila; embryonic brain; brain development; Hox genes; pair rule genes; segment polarity genes; head gap genes; retinal patterning genes; columnar patterning genes
2.  Expression of Unconventional Myosin Genes During Neuronal Development in Zebrafish 
Gene expression patterns : GEP  2007;8(3):161-170.
Neuronal migration and growth cone motility are essential aspects of the development and maturation of the nervous system. These cellular events result from dynamic changes in the organization and function of the cytoskeleton, in part due to the activity of cytoskeletal motor proteins such as myosins. Although specific myosins such as Myo2 (conventional or muscle myosin), Myo1, and Myo5 have been well characterized for roles in cell motility, the roles of the majority of unconventional (other than Myo2) myosins in cell motility events have not been investigated. To address this issue, we have undertaken an analysis of unconventional myosins in zebrafish, a premier model for studying cellular and growth cone motility in the vertebrate nervous system. We describe the characterization and expression patterns of several members of the unconventional myosin gene family. Based on available genomic sequence data, we identified 18 unconventional myosin- and 4 Myo2-related genes in the zebrafish genome in addition to previously characterized myosin (-1, -2, -3, -5, -6, -7) genes. Phylogenetic analyses indicate that these genes can be grouped into existing classifications for unconventional myosins from mouse and man. In situ hybridization analyses using EST probes for 18 of the 22 identified genes indicate that 11/18 genes are expressed in a restricted fashion in the zebrafish embryo. Specific myosins are expressed in particular neuronal or neuroepithelial cell types in the developing zebrafish nervous system, spanning the periods of neuronal differentiation and migration, and of growth cone guidance and motility.
doi:10.1016/j.gep.2007.10.010
PMCID: PMC3422748  PMID: 18078791
cytoskeleton; unconventional myosin; neuronal migration; axon guidance; growth cone motility; zebrafish; commissure; spinal cord; motor neuron; neural crest; somite; ear; eye; morphogenesis; in situ hybridization; phylogenetic tree; hindbrain; forebrain; midbrain; cranial muscles
3.  Dystrobrevin and dystrophin family gene expression in zebrafish 
Dystrophin/dystrobrevin superfamily proteins play structural and signalling roles at the plasma membrane of many cell types. Defects in them or the associated multiprotein complex cause a range of neuromuscular disorders. Members of the dystrophin branch of the family form heterodimers with members of the dystrobrevin branch, mediated by their coiled-coil domains. To determine which combinations of these proteins might interact during embryonic development, we set out to characterise the gene expression pattern of dystrophin and dystrobrevin family members in zebrafish. γ-dystrobrevin (dtng), a novel dystrobrevin recently identified in fish, is the predominant form of dystrobrevin in embryonic development. Dtng and dmd (dystrophin) have similar spatial and temporal expression patterns in muscle, where transcripts are localized to the ends of differentiated fibres at the somite borders. Dtng is expressed in the notochord while dmd is expressed in the chordo-neural hinge and then in floor plate and hypochord. In addition, dtng is dynamically expressed in rhombomeres 2 and 4-6 of the hindbrain and in the ventral midbrain. α-dystrobrevin (dtna) is expressed widely in the brain with particularly strong expression in the hypothalamus and the telencephalon; drp2 is also expressed widely in the brain. Utrophin expression is found in early pronephros and lateral line development and utrophin and dystrophin are both expressed later in the gut. β-dystrobrevin (dtnb) is expressed in the pronephric duct and widely at low levels. In summary, we find clear instances of co-expression of dystrophin and dystrobrevin family members in muscle, brain and pronephric duct development and many examples of strong and specific expression of members of one family but not the other, an intriguing finding given the presumed heterodimeric state of these molecules.
doi:10.1016/j.modgep.2007.10.004
PMCID: PMC3360968  PMID: 18042440
muscle; zebrafish; notochord; midbrain; rhombomere; gene expression; utrophin; dystrophin; dystrobrevin; drp2; dystrotelin
4.  Vestigial-like-2b (VITO-1b) and Tead-3a (Tef-5a) expression in zebrafish skeletal muscle, brain and notochord 
Gene expression patterns : GEP  2007;7(8):827-836.
The vestigial gene has been shown to control skeletal muscle formation in Drosophila and the related Vestigial-like 2 (Vgl-2) protein plays a similar role in mice. Vgl-family proteins are thought to regulate tissue-specific gene expression by binding to members of the broadly expressed Scalloped/Tef/TEAD transcription factor family. Zebrafish have at least four Vgl genes, including two Vgl-2s, and at least three TEAD genes, including two Tead3s. We describe the cloning and expression of one member from each family in the zebrafish. A novel gene, vgl-2b, with closest homology to mouse and human vgl-2, is expressed transiently in nascent notochord and in muscle fibres as they undergo terminal differentiation during somitogenesis. Muscle cells also express a TEAD-3 homologue, a possible partner of Vgl-2b, during myoblast differentiation and early fibre assembly. Tead3a is also expressed in rhombomeres, eye and epiphysis regions.
doi:10.1016/j.modgep.2007.08.001
PMCID: PMC3360971  PMID: 17916448
muscle; adaxial; zebrafish; vestigial-like; transcription enhancer factor; TEAD domain
5.  Mrf4 (myf6) is dynamically expressed in differentiated zebrafish skeletal muscle 
Gene expression patterns : GEP  2007;7(7):738-745.
Mrf4 (Myf6) is a basic helix-loop-helix (bHLH) myogenic regulatory transcription factor (MRF) family which also contains Myod, Myf5 and myogenin. Mrf4 is implicated in commitment of amniote cells to skeletal myogenesis and is also abundantly expressed in many adult muscle fibres. The specific role of Mrf4 is unclear both because mrf4 null mice are viable, suggesting redundancy with other MRFs, and because of genetic interactions at the complex mrf4/myf5 locus. We report the cloning and expression of an mrf4 gene from zebrafish, Danio rerio, which shows conservation of linkage to myf5. Mrf4 mRNA accumulates in a subset of terminally differentiated muscle fibres in parallel with myosin protein in the trunk and fin. Although most, possibly all, trunk muscle expresses mrf4, the level of mRNA is dynamically regulated. No expression is detected in muscle precursor cell populations prior to myosin accumulation. Moreover, mrf4 expression is not detected in head muscles, at least at early stages. As fish mature, mrf4 expression is pronounced in slow muscle fibres.
doi:10.1016/j.modgep.2007.06.003
PMCID: PMC3001336  PMID: 17638597
mrf4; muscle; zebrafish; muscle pioneers; muscle fibre; fin; myod; myogenin; mylz2; gene expression, craniofacial
6.  Expression of the G protein gamma T1 subunit during zebrafish development 
Gene expression patterns : GEP  2007;7(5):574-583.
Here, we report the identification and expression analysis of the zebrafish G protein gamma T1 subunit gene (gngT1) during development. Similar to its human and mouse homologs, we confirm zebrafish gngT1 is expressed in the developing retina, where its transcription overlaps with the photoreceptor cell-specific marker, rhodopsin (rho). Surprisingly, we also show zebrafish gngT1 is expressed in the dorsal diencephalon, where its transcription overlaps with the pineal specific markers, arylalkylamine N-acetyltransferase-2 (annat-2) and extra-ocular rhodopsin (exorh). Analysis of the proximal promoter sequence of the zebrafish gngT1 gene identifies several conserved binding sites for the cone-rod homeobox/orthodenticle (Crx/Otx) homeodomain family of transcription factors. Using a morpholino antisense approach in zebrafish, we show that targeted knockdown of otx5 potently suppresses gngT1 expression in the pineal gland, whereas knockdown of crx markedly reduces gngT1 expression in the retina. Taken together, these data indicate that pineal- and retinal-specific expression of the gngT1 gene are controlled by different transcription factors and exogenous signals.
doi:10.1016/j.modgep.2007.01.003
PMCID: PMC2754307  PMID: 17306630
Zebrafish; G protein; gngT1; Signal transduction; Rhodopsin; Exo-rhodopsin; Pineal gland; Retina; Photoreceptor cells
7.  Dynamic gene expression of Lin-28 during embryonic development in mouse and chicken 
Gene expression patterns : GEP  2007;8(3):155-160.
The Caenorhabditis elegans heterochronic gene lin-28 regulates developmental timing in the nematode trunk. We report the dynamic expression patterns of Lin-28 homologues in mouse and chick embryos. Whole mount in situ hybridization revealed specific and intriguing expression patterns of Lin-28 in the developing mouse and chick limb bud. Mouse Lin-28 expression was detected in both the fore-limb and hindlimb at E9.5, but disappeared from the forelimb at E10.5, and finally from the forelimb and hindlimb at E11.5. Chicken Lin-28, which was first detected in the limb primordium at stage 15/16, was also downregulated as the stage proceeded. The amino acid sequences of mouse and chicken Lin-28 genes are highly conserved and the similar expression patterns of Lin-28 during limb development in mouse and chicken suggest that this heterochronic gene is also conserved during vertebrate limb development.
doi:10.1016/j.gep.2007.11.001
PMCID: PMC2262948  PMID: 18077221
Heterochronic gene; Whole mount in situ hybridization; Mouse; Chick; Limb bud; Lin-28; MicroRNAs; Developmental timing; Dynamic expression; Embryo
8.  An in situ hybridization-based screen for heterogeneously expressed genes in mouse ES cells 
Gene expression patterns : GEP  2007;8(3):181-198.
We previously reported that Zscan4 showed heterogeneous expression patterns in mouse embryonic stem (ES) cells. To identify genes that show similar expression patterns, we carried out high-throughput in situ hybridization assays on ES cell cultures for 244 genes. Most of the genes are involved in transcriptional regulation, and were selected using microarray-based comparisons of gene expression profiles in ES and embryonal carcinoma (EC) cells versus differentiated cell types. Pou5f1 (Oct4, Oct3/4) and Krt8 (EndoA) were used as controls. Hybridization signals were detected on ES cell colonies for 147 genes (60%). The majority (136 genes) of them showed relatively homogeneous expression in ES cell colonies. However, we found that two genes unequivocally showed Zscan4-like spotted expression pattern (spot-in-colony pattern; Whsc2 and Rhox9). We also found that nine genes showed relatively heterogeneous expression pattern (mosaic-in-colony pattern: Zfp42/Rex1, Rest, Atf4, Pa2g4, E2f2, Nanog, Dppa3/Pgc7/Stella, Esrrb, and Fscn1). Among these genes, Zfp42/Rex1 showed unequivocally heterogeneous expression in individual ES cells prepared by the CytoSpin. These results show the presence of different types or states of cells within ES cell cultures otherwise thought to be undifferentiated and homogeneous, suggesting a previously unappreciated complexity in ES cell cultures.
doi:10.1016/j.gep.2007.10.009
PMCID: PMC2238805  PMID: 18178135
ES cells; EC cells; pluripotent stem cells; heterogeneous gene expression; homogeneous gene expression; Zscan4; Pou5f1; Oct4; Oct3/4; Krt8; EndoA; Whsc2; Nelfa; Rhox9; Zfp42; Rex1; Rest; Zfp42; Rex1; Rest; Atf4; Pa2g4; E2f2; Nanog; Dppa3; Pgc7; Stella; Esrrb; Fscn1
9.  A Web Based Resource Characterizing the Zebrafish Developmental Profile of over 16,000 transcripts 
Gene expression patterns : GEP  2007;8(3):171-180.
Using a spotted 65-mer oligonucleotide microarray, we have characterized the developmental expression profile from mid-gastrulation (75% epiboly) to 5 days post-fertilization (dpf) for >16,000 unique transcripts in the zebrafish genome. Microarray profiling data sets are often immense, and one challenge is validating the results and prioritizing genes for further study. The purpose of the current study was to address such issues, as well as to generate a publicly available resource for investigators to examine the developmental expression profile of any of the over 16,000 zebrafish genes on the array. On the chips, there are 16,459 printed spots corresponding to 16,288 unique transcripts and 172 β-actin (AF025305) spots spatially distributed throughout the chip as a positive control. We have collected 55 microarray gene expression profiling results from various zebrafish laboratories and created a Perl/CGI-based software tool (http://serine.umdnj.edu/~ouyangmi/cgi-bin/zebrafish/profile.htm) for researchers to look for the expression patterns of their gene of interest. Users can search for their genes of interest by entering the accession numbers or the nucleotide sequences and the expression profiling will be reported in the form of expression intensities versus time-course graphical displays. In order to validate this web tool, we compared seventy-four genes’ expression results between our web tool and the in situ hybridization results from Thisse et al. (2004) as well as those reported by Mathavan et al. (2005). The comparison indicates the expression patterns are 80% and 75% in agreement between our web resource with the in situ database (Thisse et al. 2004) and with those reported by Mathavan et al. (2005), respectively. Those genes that conflict between our web tool and the in situ database either have high sequence similarity with other genes or the in situ probes are not reliable. Among those genes that disagree between our web tool and those reported by Mathavan et al. (2005), 93% of the genes are in agreement between our web tool and the in situ database, indicating our web tool results are quite reliable. Thus, this resource provides a user-friendly web based platform for researchers to determine the developmental profile of their gene of interest and to prioritize genes identified in microarray analyses by their developmental expression profile.
doi:10.1016/j.gep.2007.10.011
PMCID: PMC2253684  PMID: 18068546
10.  Expression and functional analysis of a novel Fusion Competent Myoblast specific GAL4 driver 
In the Drosophila embryo, body wall muscles are formed by the fusion of two cell types, Founder Cells (FCs) and Fusion Competent Myoblasts (FCMs). Using an enhancer derived from the Dmef2 gene ([C/D]*), we report the first GAL4 driver specifically expressed in FCMs. We have determined that this GAL4 driver causes expression in a subset of FCMs and, upon fusion, in developing myotubes from stage 14 onwards. In addition, we have shown that using this Dmef2-5x[C/D]*-GAL4 driver to express dominant negative Rac in only FCMs causes a partial fusion block. This novel GAL4 driver will provide a useful reagent to study Drosophila myoblast fusion and muscle differentiation.
doi:10.1016/j.modgep.2007.10.002
PMCID: PMC2268213  PMID: 17988956
Muscle; Fusion Competent Myoblast; Myotube; Drosophila; Dmef2; Lmd; Rac; Myoblast; Fusion
11.  The PcG Gene Sfmbt2 is Paternally Expressed in Extraembryonic Tissues 
Gene expression patterns : GEP  2007;8(2):107-116.
Genomic imprinting has dramatic effects on placental development, as has been clearly observed in interspecific hybrid, somatic cell nuclear transfer, and uniparental embryos. In fact, the earliest defects in uniparental embryos are evident first in the extraembryonic trophoblast. We performed a microarray comparison of gynogenetic and androgenetic mouse blastocysts, which are predisposed to placental pathologies, to identify imprinted genes. In addition to identifying a large number of known imprinted genes, we discovered that the Polycomb group (PcG) gene Sfmbt2 is imprinted. Sfmbt2 is expressed preferentially from the paternal allele in early embryos, and in later stage extraembryonic tissues. A CpG island spanning the transcriptional start site is differentially methylated on the maternal allele in e14.5 placenta. Sfmbt2 is located on proximal chromosome 2, in a region known to be imprinted, but for which no genes had been identified until now. This possibly identifies a new imprinted domain within the murine genome. We further demonstrate that murine SFMBT2 protein interacts with the transcription factor YY1, similar to the Drosophila PHO-RC.
doi:10.1016/j.modgep.2007.09.005
PMCID: PMC2220043  PMID: 18024232
Genomic Imprinting; Sfmbt2; PcG gene; Extraembryonic tissues; placenta; MMU2; YY1; microarrays; uniparental embryos
12.  The Slit receptor Robo1 is predominantly expressed via the Dutt1 alternative promoter in pioneer neurons in the embryonic mouse brain and spinal cord 
Gene expression patterns : GEP  2007;7(8):837-845.
Robo1 is a member of the Roundabout (Robo) family of receptors for the Slit axon guidance cues. In mice (and humans), the Robo1 locus has alternative promoters producing two transcript isoforms, Robo1 and Dutt1. These isoforms have unique 5′ termini, predicted to encode distinct N-terminal amino acids, but share the rest of their 3′ exons. To determine the spatial expression of the Robo1 and Dutt1 isoforms, we generated isoform-specific RNA probes, and carried out in situ hybridization on E10.5 mouse embryos, the stage in early neuron differentiation when many major axon pathways are established. The two isoforms had distinct expression patterns that partially overlapped. Dutt1 was the predominant isoform, with widespread expression in regions of post-mitotic neurons and neuroepithelial cells. The Robo1 isoform had a distinct expression pattern restricted to subsets of neurons, many of which were Dutt1-negative. Dutt1 was the main isoform expressed in spinal cord commissural neurons. For both probes, the main hybridization signal was limited to two spots in the nuclei of individual cells. This study shows distinct expression patterns for the Dutt1 and Robo1 alternative promoters in the embryonic nervous system.
doi:10.1016/j.modgep.2007.07.004
PMCID: PMC2080859  PMID: 17826360
axon guidance; neuron; Robo; Slit; longitudinal axon; commissural axon; dorsal root ganglion
13.  Expression Analysis of nha-oc/NHA2: a Novel Gene Selectively Expressed in Osteoclasts 
Gene expression patterns : GEP  2007;7(8):846-851.
Bone resorption by osteoclasts is required for normal bone remodeling and reshaping of growing bones. Excessive resorption is an important pathologic feature of many diseases, including osteoporosis, arthritis, and periodontitis (Abu-Amer, 2005). On the other hand, deficient resorption leads to osteopetrosis which is characterized by increased bone mass and may lead to bone deformities or in severe cases to death (Blair and Athanasou, 2004; Del Fattore et al., 2006).
Recently, we identified a gene, nha-oc/NHA2, which is strongly up regulated during RANKL-induced osteoclast differentiation in vitro and in vivo. nha-oc/NHA2 encodes a novel cation/proton exchanger that is strongly expressed in osteoclasts. The purpose of this work was to further validate the restricted expression of nha-oc/NHA2 in osteoclasts by in situ hybridization. Our results showed that nha-oc is expressed predominantly in bone. In the head, expression was found in the supraoccipitale bone, calvarium, mandible, and maxilla. Furthermore, nha-oc positive cells co-express the osteoclast markers TRAP and cathepsin k, confirming nha-oc/NHA2 osteoclast localization. However, only a subset of cathepsin k-expressing cells is positive for nha-oc/NHA2, suggesting that nha-oc is expressed by terminally differentiated osteoclasts.
doi:10.1016/j.modgep.2007.07.002
PMCID: PMC2271150  PMID: 17698421
Osteoclast Specific; Cation Proton Exchanger; Bone Resorption
14.  Expression of COUP-TF-interacting protein 2 (CTIP2) in mouse skin during development and in adulthood 
Gene expression patterns : GEP  2007;7(7):754-760.
COUP-TF-interacting protein 2 (CTIP2), also known as Bcl11b, is a transcriptional regulatory protein that is highly expressed in and plays a critical role(s) during development of T lymphocytes and the central nervous system. We demonstrate herein that CTIP2 is also highly expressed in mouse skin during embryogenesis and in adulthood as revealed by immunohistochemical analyses. CTIP2 expression in the ectoderm was first detected at embryonic day 10.5 (E10.5), and became increasingly restricted to proliferating cells of the basal cell layer of the developing epidermis in later stages of fetal development and in adult skin. In addition, CTIP2 expression was also detected in some cells of the suprabasal layer of the developing epidermis, as well as in developing and mature hair follicles. Relatively fewer cells of the developing dermal component of skin were found to express CTIP2, and the adult dermis was devoid of CTIP2 expression. Some, but not all, of the cells present within hair follicle bulge were found to co-express CTIP2, keratin K15, and CD34, indicating that a subset of K15+ CD34+ skin stem cells may express CTIP2. Considered together, these findings suggest that CTIP2 may play a role(s) in skin development and/or homeostasis.
doi:10.1016/j.modgep.2007.06.002
PMCID: PMC2063996  PMID: 17631058
COUP-TF-interacting protein 2; Bcl11b; nuclear receptor; Transcription; expression; zinc finger; skin; epidermis; dermis; ectoderm; mesoderm; keratinocyte; stratification; development; stem cells; proliferation; differentiation; morphogenesis; basal cell; suprabasal cell; hair bulb; hair follicle; hair bulge; immunohistochemistry; in situ hybridization; marker; mouse; embryo; K10; K14; K15; Ki67; CD34
15.  Expression of LHX3 and SOX2 during Mouse Inner Ear Development 
Gene expression patterns : GEP  2007;7(7):798-807.
A cascade of transcription factors is believed to regulate the coordinate differentiation of primordial inner ear cells into the subtypes of hair cells and supporting cells. While candidate genes involved in this process have been identified, the temporal and spatial patterns of expression of many of these have not been carefully described during the extended period of inner ear development and functional maturation. We systematically examined the expression of two such transcription factors, LHX3 and SOX2, from the time of hair cell terminal mitoses into adulthood. We show that LHX3 is expressed specifically in auditory and vestibular hair cells soon after terminal mitoses and persists into the adult in vestibular hair cells. While SOX2 expression is widespread in the inner ear sensory epithelia prior to hair cell differentiation, it has a unique pattern of expression in the mature auditory and vestibular organs.
doi:10.1016/j.modgep.2007.05.002
PMCID: PMC2043117  PMID: 17604700
LHX; LIM-homeodomain; MATH-1; inner ear; cochlea; ATOH1; SOX; hmg box; hair cell; deafness; HLH; bHLH; genetics
16.  Expression patterns of alternative transcripts of the zebrafish olfactomedin 1 genes 
Gene expression patterns : GEP  2007;7(7):723-729.
Olfactomedin 1 (Olfm1) is a founding member of the family of olfactomedin domain-containing proteins. It is a secreted protein that performs different roles in different species. Although the molecular mechanisms of Olfm1 action are not known, its possible roles include the regulation of neural crest cell production, neuronal differentiation and ischemic neuronal death in adult. Two zebrafish olfm1 gene (olfm1a and olfm1b) located on chromosomes 5 and 21 were identified in zebrafish genome. Four different transcripts are produced from each olfm1 gene. The distribution of these transcripts in the course of zebrafish early development was studied by in situ hybridization and quantitative RT-PCR. Different variants of olfm1 mRNA were present mainly in neurogenic tissues and demonstrated overlapping expression patterns.
doi:10.1016/j.modgep.2007.06.005
PMCID: PMC2081154  PMID: 17681890
olfactomedin; zebrafish; development; in situ hybridization; motor neurons; Rohon-Beard neurons; trigeminal ganglia; neural crest
17.  Characterization of the mid-foregut transcriptome identifies genes regulated during lung bud induction 
Gene expression patterns : GEP  2007;8(2):124-139.
To identify genes expressed during initiation of lung organogenesis, we generated transcriptional profiles of the prospective lung region of the mouse foregut (mid-foregut) microdissected from embryos at three developmental stages between embryonic day 8.5 (E8.5) and E9.5. This period spans from lung specification of foregut cells to the emergence of the primary lung buds. We identified a number of known and novel genes that are temporally regulated as the lung bud forms. Genes that regulate transcription, including DNA binding factors, co-factors, and chromatin remodeling genes, are the main functional groups that change during lung bud formation. Members of key developmental transcription and growth factor families, not previously described to participate in lung organogenesis, are expressed in the mid-foregut during lung bud induction. These studies also show early expression in the mid-foregut of genes that participate in later stages of lung development. This characterization of the mid-foregut transcriptome provides new insights into molecular events leading to lung organogenesis.
doi:10.1016/j.modgep.2007.09.003
PMCID: PMC2440337  PMID: 18023262
Lung; development; organogenesis; foregut; endoderm; embryo; mouse; microarray; RNA amplification; gene expression; real time PCR; laser capture microdissection; transcription factors; chromatin remodeling; Fox; Notch
18.  Expression and regulation of the zinc finger transcription factor Churchill during zebrafish development 
Gene expression patterns : GEP  2007;7(6):645-650.
During gastrulation dynamic cell movements establish the germ layers and shape the body axis of the vertebrate embryo. The zinc finger protein Churchill (chch) has been proposed to be a key regulator of these movements. We examined the expression pattern of chch in zebrafish and studied the regulation of chch by FGF signaling. We observed zygotic expression of chch during early cleavage stages. Two lines of evidence demonstrate that chch is zygotically expressed prior to the mid-blastula transition. First, blocking transcription during early cleavage stages represses chch expression. Second, endogenous levels of chch transcripts increase between 1-cell and 16-cell embryos. chch remains widely expressed during blastula and gastrula stages but scattered cells express higher levels of chch. By somitogenesis, chch is expressed in the ventral-most cells of the embryo adjacent to the yolk. In addition, transcripts are also observed in superficial cells on the surface of the yolk, in presumptive mucous cells and keratinocytes. By 30 hpf transcripts are observed in anterior neural tissue and ventral cells adjacent to the yolk. Over the next three days chch expression is indistinct until 4 dpf when we observe expression in the pharynx and gut. We show that activation of FGF signaling during gastrulation is sufficient to induce chch expression. In addition, we demonstrate that blocking FGF signaling between the 4-cell and shield stages represses chch expression.
doi:10.1016/j.modgep.2007.04.002
PMCID: PMC1976285  PMID: 17521969
19.  Pax6 is misexpressed in Sox1 null lens fiber cells 
Gene expression patterns : GEP  2007;7(5):606-613.
Sox1 null lens fiber cells fail to elongate and have disrupted expression of gamma crystallin. We have evaluated the expression of Sox1 and Pax6 proteins during critical stages of lens morphogenesis, with particular focus on fiber cell differentiation. While Pax6 and Sox1 are co-expressed during early stages of fiber cell differentiation, Sox1 up-regulation coincides temporally with the down-regulation of Pax6, and these proteins therefore display a striking inverse expression pattern in the lens fiber cell compartment. Furthermore, Pax6 is inappropriately expressed in the fiber cells of Sox1 null mice and the Pax6 target, α5 integrin, is simultaneously misexpressed. Finally, we demonstrate a genetic interaction between Sox1 and Pax6, as Sox1 heterozygosity partially rescues the diameter of Pax6Sey lenses by increasing the number of cells in the fiber cell compartment.
doi:10.1016/j.modgep.2007.01.001
PMCID: PMC2246053  PMID: 17306631
Sox1; Pax6; α5 integrin; cataract; lens; fiber cell; anterior epithelial layer
20.  A high-resolution anatomical ontology of the developing murine genitourinary tract 
Gene expression patterns : GEP  2007;7(6):680-699.
Cataloguing gene expression during development of the genitourinary tract will increase our understanding not only of this process but also of congenital defects and disease affecting this organ system. We have developed a high-resolution ontology with which to describe the subcompartments of the developing murine genitourinary tract. This ontology incorporates what can be defined histologically and begins to encompass other structures and cell types already identified at the molecular level. The ontology is being used to annotate in situ hybridisation data generated as part of the Genitourinary Development Molecular Anatomy Project (GUDMAP), a publicly available data resource on gene and protein expression during genitourinary development. The GUDMAP ontology encompasses Theiler stage (TS) 17 to 27 of development as well as the sexually mature adult. It has been written as a partonomic, text-based, hierarchical ontology that, for the embryological stages, has been developed as a high-resolution expansion of the existing Edinburgh Mouse Atlas Project (EMAP) ontology. It also includes group terms for well-characterised structural and/or functional units comprising several sub-structures, such as the nephron and juxtaglomerular complex. Each term has been assigned a unique identification number. Synonyms have been used to improve the success of query searching and maintain wherever possible existing EMAP terms relating to this organ system. We describe here the principles and structure of the ontology and provide representative diagrammatic, histological, and whole mount and section RNA in situ hybridisation images to clarify the terms used within the ontology. Visual examples of how terms appear in different specimen types are also provided.
doi:10.1016/j.modgep.2007.03.002
PMCID: PMC2117077  PMID: 17452023
genitourinary development; renal development; kidney development; urinary development; reproductive development; kidney; gonad; bladder; ureter; urethra; genital tubercle; ovary; testis; congenital defects; gene expression; ontology; annotation; database; anatomy; atlas of development; partonomic ontology; RNA in situ hybridisation
21.  Cloning of zebrafish nkx6.2 and a comprehensive analysis of the conserved transcriptional response to Hedgehog/Gli signaling in the zebrafish neural tube 
Gene expression patterns : GEP  2007;7(5):596-605.
Sonic Hedgehog (Shh) signaling helps pattern the vertebrate neural tube, in part by regulating the dorsal/ventral expression of a number of homeodomain containing transcription factors. These Hh responsive genes have been divided into two classes, with Class II genes being activated by Hh signaling and Class I genes being repressed by Hh signaling. While the transcriptional response to varying Hh levels is well defined in chick and mouse, it is only partially described in zebrafish, despite the fact that zebrafish has emerged as a powerful genetic system for the study of neural patterning. To better characterize the Hh response in the zebrafish neural tube, we cloned the zebrafish Class II Hh target genes nkx2.9 and nkx6.2. We then analyzed the expression of a number of Class I and Class II Hh responsive genes in wild type, Hh mutant, and Hh over-expressing zebrafish embryos. We show that expression of Class I and Class II genes is highly conserved in the vertebrate neural tube. Further, ventral-most Class II gene expression was completely lost in all Hh pathway mutants analyzed, indicating high levels of Hh signaling are blocked in all of these mutants. In contrast, more dorsally expressed genes were variably affected in different Hh pathway mutants, indicating mid-levels of Hh signaling are differentially affected. This comprehensive expression study provides an important tool for the characterization of Hh signaling in zebrafish and provides a sensitive assay for determining the degree to which newly identified zebrafish mutants affect Hh signaling.
doi:10.1016/j.modgep.2007.01.002
PMCID: PMC2043473  PMID: 17307034
dbx1a; dbx2; hlx1; hlxb9; irx1a; irx3a; irx5; nkx2.2a; nkx2.9; nkx6.1; nkx6.2; pax3; pax6a; pax7; chameleon; detour; slow muscle omitted; you-too; cyclopamine; floorplate; motor neurons
22.  Characterization of Bcor Expression in Mouse Development 
Gene expression patterns : GEP  2007;7(5):550-557.
Mutation of the gene encoding the transcriptional corepressor BCOR results in the X-linked disorder Oculofaciocardiodental Syndrome (OFCD or MCOPS2). Female OFCD patients suffer from severe ocular, craniofacial, cardiac and digital developmental defects and males do not survive through gestation. BCOR can mediate transcriptional repression by the oncoprotein BCL6 and has the ability to reduce transcriptional activation by AF9, a known mixed-lineage leukemia (MLL) fusion partner. The essential role of BCOR in development and its ability to modulate activity of known oncogenic proteins prompted us to determine the expression profile of Bcor during mouse development. Identification of independently transcribed exons in the 5′ untranslated region of Bcor suggests that three independent promoters control the expression of Bcor in mice. Although Bcor is widely expressed in adult mouse tissues, analysis of known spliced isoforms in the coding region of Bcor reveals differential isoform usage. Whole mount in situ hybridization of mouse embryos shows that Bcor is strongly expressed in the extraembryonic tissue during gastrulation and expression significantly increases throughout the embryo after embryonic turning. During organogenesis and fetal stages Bcor is differentially expressed in multiple tissue lineages, with a notable presence in the developing nervous system. Strikingly, we observed that Bcor expression in the eye, brain, neural tube and branchial arches correlates with tissues affected in OFCD patients.
doi:10.1016/j.modgep.2007.01.006
PMCID: PMC2002546  PMID: 17344103
Bcor; Oculofaciocardiodental syndrome; MCOPS2; extraembryonic

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