Biomedical subjects

Andrew J Latimer

Publications and source records attributed to Andrew J Latimer.

6 recordsLinked to original sources

PubMed2006

In vivo time-lapse imaging shows dynamic oligodendrocyte progenitor behavior during zebrafish development.

Myelinating oligodendrocytes arise from migratory and proliferative oligodendrocyte progenitor cells (OPCs). Complete myelination requires that oligodendrocytes be uniformly distributed and form numerous, periodically spaced membrane sheaths along the entire length of target axons. Mechanisms that determine spacing of oligodendrocytes and their myelinating processes are not known. Using in vivo time-lapse confocal microscopy, we show that zebrafish OPCs continuously extend and retract numerous filopodium-like processes as they migrate and settle into their final positions. Process remodeling and migration paths are highly variable and seem to be influenced by contact with neighboring OPCs. After laser ablation of oligodendrocyte-lineage cells, nearby OPCs divide more frequently, orient processes toward the ablated cells and migrate to fill the unoccupied space. Thus, process activity before axon wrapping might serve as a surveillance mechanism by which OPCs determine the presence or absence of nearby oligodendrocyte-lineage cells, facilitating uniform spacing of oligodendrocytes and complete myelination.

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PubMed2006

Notch signaling regulates midline cell specification and proliferation in zebrafish.

Notochord and floor plate cells are sources of molecules that pattern tissues near the midline, including the spinal cord. Hypochord cells are also found at the midline of anamniote embryos and are important for aorta development. Delta-Notch signaling regulates midline patterning in the dorsal organizer by inhibiting notochord formation and promoting hypochord and possibly floor plate development, but the precise mechanisms by which this regulation occurs are unknown. We demonstrate here that floor plate and hypochord cells arise from distinct regions of the zebrafish shield. Blocking Notch signaling during gastrulation entirely prevented hypochord specification but only reduced the number of floor plate cells that developed compared to control embryos. In contrast, elevation of Notch signaling at the beginning of gastrulation caused expansion of hypochord at the expense of notochord, but floor plate was not affected. A cell proliferation assay revealed that Notch signaling maintains dividing floor plate progenitors. Together, our results indicate that Notch signaling regulates allocation of appropriate numbers of different midline cells by different mechanisms.

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PubMed2005

her9 promotes floor plate development in zebrafish.

Notochord, floor plate, and in anamniotes hypochord, are vertebrate embryonic midline structures that are the sources of molecules that pattern the nervous system, somites, and dorsal aorta. Midline precursor cells arise from the dorsal organizer during gastrulation, and Notch signaling is an important regulator of midline cell fate specification. To understand fully how Notch signaling regulates midline development, we investigated the role of potential Notch target genes. We show here that midline precursors express her9, a member of the hairy/Enhancer of split gene family. Although her9 inhibits notochord development and promotes floor plate specification, her9 expression in floor plate cells appears not to require Notch signaling. We show that, instead, her9 is a downstream effector of Nodal signaling for floor plate specification.

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PubMed2005

Inositol polyphosphates regulate zebrafish left-right asymmetry.

Vertebrate body plans have a conserved left-right (LR) asymmetry manifested in the position and anatomy of the heart, visceral organs, and brain. Recent studies have suggested that LR asymmetry is established by asymmetric Ca2+ signaling resulting from cilia-driven flow of extracellular fluid across the node. We report here that inositol 1,3,4,5,6-pentakisphosphate 2-kinase (Ipk1), which generates inositol hexakisphosphate, is critical for normal LR axis determination in zebrafish. Zebrafish embryos express ipk1 symmetrically during gastrulation and early segmentation. ipk1 knockdown by antisense morpholino oligonucleotide injection randomized LR-specific gene expression and organ placement, effects that were associated with reduced intracellular Ca2+ flux in cells surrounding the ciliated Kupffer's vesicle, a structure analogous to the mouse node. Our data suggest that the pathway for inositol hexakisphosphate production is a key regulator of asymmetric Ca(2+) flux during LR specification.

Amino Acid Sequence↗

PubMed2003

lunatic fringe regulates Delta-Notch induction of hypochord in zebrafish.

Cells that occupy the midline of vertebrate embryos arise from a common population of precursors. Several lines of evidence indicate that Delta-Notch signaling regulates specification of midline precursors for different fates. We show that zebrafish midline precursors transiently express lunatic fringe, which encodes a glycosyltransferase that modifies Notch activity in response to its ligands, and that lunatic fringe function is required for Delta-Notch-mediated induction of hypochord cells at the lateral borders of the midline precursor domain.

Animals↗

PubMed2002

Delta-Notch signaling induces hypochord development in zebrafish.

Different cell types that occupy the midline of vertebrate embryos originate within the Spemann-Mangold or gastrula organizer. One such cell type is hypochord, which lies ventral to notochord in anamniote embryos. We show that hypochord precursors arise from the lateral edges of the organizer in zebrafish. During gastrulation, hypochord precursors are closely associated with no tail-expressing midline precursors and paraxial mesoderm, which expresses deltaC and deltaD. Loss-of-function experiments revealed that deltaC and deltaD were required for her4 expression in presumptive hypochord precursors and for hypochord development. Conversely, ectopic, unregulated Notch activity blocked no tail expression and promoted her4 expression. We propose that Delta signaling from paraxial mesoderm diversifies midline cell fate by inducing a subset of neighboring midline precursors to develop as hypochord, rather than as notochord.

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