Three-dimensional multi-gene expression maps reveal cell fate changes associated with laterality reversal of zebrafish habenula.

The conserved bilateral habenular nuclei (HA) in vertebrate diencephalon develop into compartmentalized structures containing neurons derived from different cell lineages. Despite extensive studies demonstrated that zebrafish larval HA display distinct left-right (L-R) asymmetry in gene expression and connectivity, the spatial gene expression domains were mainly obtained from two-dimensional (2D) snapshots of colorimetric RNA in situ hybridization staining which could not properly reflect different HA neuronal lineages constructed in three-dimension (3D). Combing the tyramide-based fluorescent mRNA in situ hybridization, confocal microscopy and customized imaging processing procedures, we have created spatial distribution maps of four genes for 4-day-old zebrafish and in sibling fish whose L-R asymmetry was spontaneously reversed.

Control of Wnt5b secretion by Wntless modulates chondrogenic cell proliferation through fine-tuning fgf3 expression.

Wnts and Fgfs regulate various tissues development in vertebrates. However, how regional Wnt or Fgf activities are established and how they interact in any given developmental event is elusive. Here, we investigated the Wnt-mediated craniofacial cartilage development in zebrafish and found that fgf3 expression in the pharyngeal pouches is differentially reduced along the anteroposterior axis in wnt5b mutants and wntless (wls) morphants, but its expression is normal in wnt9a and wnt11 morphants.

Protein tyrosine phosphatase receptor type O (Ptpro) regulates cerebellar formation during zebrafish development through modulating Fgf signaling.

Protein activities controlled by receptor protein tyrosine phosphatases (RPTPs) play comparably important roles in transducing cell surface signals into the cytoplasm by protein tyrosine kinases. Previous studies showed that several RPTPs are involved in neuronal generation, migration, and axon guidance in Drosophila, and the vertebrate hippocampus, retina, and developing limbs. However, whether the protein tyrosine phosphatase type O (ptpro), one kind of RPTP, participates in regulating vertebrate brain development is largely unknown.

Drosophila suppressor of sable protein [Su(s)] promotes degradation of aberrant and transposon-derived RNAs.

RNA-binding proteins act at various stages of gene expression to regulate and fine-tune patterns of mRNA accumulation. One protein in this class is Drosophila Su(s), a nuclear protein that has been previously shown to inhibit the accumulation of mutant transcripts by an unknown mechanism. Here, we have identified several additional RNAs that are downregulated by Su(s).

Selective asymmetry in a conserved forebrain to midbrain projection.

How the left and right sides of the brain acquire anatomical and functional specializations is not well understood. The zebrafish has proven to be a useful model to explore the genetic basis of neuroanatomical asymmetry in the developing forebrain. The dorsal diencephalon or epithalamus consists of the asymmetric pineal complex and adjacent paired nuclei, the left and right medial habenulae, which in zebrafish larvae, exhibit differences in their size, neuropil density and patterns of gene expression.

Neuropilin asymmetry mediates a left-right difference in habenular connectivity.

The medial habenular nuclei of the zebrafish diencephalon, which lie bilateral to the pineal complex, exhibit left-right differences in their neuroanatomy, gene expression profiles and axonal projections to the unpaired midbrain target--the interpeduncular nucleus (IPN). Efferents from the left habenula terminate along the entire dorsoventral extent of the IPN, whereas axons from the right habenula project only to the ventral IPN. How this left-right difference in connectivity is established and the factors involved in differential target recognition are unknown.

Directional asymmetry of the zebrafish epithalamus guides dorsoventral innervation of the midbrain target.

The zebrafish epithalamus, consisting of the pineal complex and flanking dorsal habenular nuclei, provides a valuable model for exploring how left-right differences could arise in the vertebrate brain. The parapineal lies to the left of the pineal and the left habenula is larger, has expanded dense neuropil, and distinct patterns of gene expression from the right habenula. Under the influence of Nodal signaling, positioning of the parapineal sets the direction of habenular asymmetry and thereby determines the left-right origin of habenular projections onto the midbrain target, the interpeduncular nucleus (IPN).

Suppressor of sable, a putative RNA-processing protein, functions at the level of transcription.

The Drosophila melanogaster su(s) gene product negatively regulates the expression of mutant alleles with transposon insertions in the 5'-transcribed region by an unknown mechanism. We have investigated here su(s) function through in vivo structure-function analysis, heterologous reporter gene assays, and in vivo transcriptional induction experiments. We have shown that mutations of two arginine-rich motifs (ARMs), an acidic region, or two CCCH zinc fingers affect the ability of Su(s) to downregulate the expression of an insertion mutant allele and to autoregulate genomic su(s) transgenes.