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Biomedical subjects

Richard B Anderson

Publications and source records attributed to Richard B Anderson.

9 recordsLinked to original sources
PubMed2007

Effect of Gdnf haploinsufficiency on rate of migration and number of enteric neural crest-derived cells.

The enteric nervous system arises predominantly from vagal level neural crest cells that migrate into the foregut and then colonize the entire length of the gastrointestinal tract. Previous studies have demonstrated that glial cell line-derived neurotrophic factor (GDNF) promotes the migration of enteric neural crest-derived cells (ENCs) in vitro, but a role for GDNF in the migration of ENCs in vivo has yet to be demonstrated. In this study, the effects of Gdnf haploinsufficiency on ENC rate of migration and number during mid embryonic development were examined. Although the entire gut of embryonic Gdnf(+/-) mice was colonized, a significant delay in the migration of ENCs along the embryonic hindgut was found. However, significant effects of Gdnf haploinsufficiency on ENC number were detected before the stage at which migration defects were first evident. As previous studies have shown a relationship between ENC number and migration, the effects of Gdnf haploinsufficiency on migration may be due to an indirect effect on cell number and/or a direct effect of GDNF on ENC migration. Gdnf haploinsufficiency did not cause any detectable change in the rate of neuronal differentiation of ENCs.

Animals↗
PubMed2006

The Wnt receptor Ryk is required for Wnt5a-mediated axon guidance on the contralateral side of the corpus callosum.

Ryk (receptor related to tyrosine kinase) has been shown to be a novel Wnt receptor in both Caenorhabditis elegans and Drosophila melanogaster. Recently, Ryk-Wnt interactions were shown to guide corticospinal axons down the embryonic mouse spinal cord. Here we show that, in Ryk-deficient mice, cortical axons project aberrantly across the major forebrain commissure, the corpus callosum. Many mouse mutants have been described in which loss-of-function mutations result in the inability of callosal axons to cross the midline, thereby forming Probst bundles on the ipsilateral side. In contrast, loss of Ryk does not interfere with the ability of callosal axons to cross the midline but impedes their escape from the midline into the contralateral side. Therefore, Ryk(-/-) mice display a novel callosal guidance phenotype. We also show that Wnt5a acts as a chemorepulsive ligand for Ryk, driving callosal axons toward the contralateral hemisphere after crossing the midline. In addition, whereas callosal axons do cross the midline in Ryk(-/-) embryos, they are defasciculated on the ipsilateral side, indicating that Ryk also promotes fasciculation of axons before midline crossing. In summary, this study expands the emerging role for Wnts in axon guidance and identifies Ryk as a key guidance receptor in the establishment of the corpus callosum. Our analysis of Ryk function further advances our understanding of the molecular mechanisms underlying the formation of this important commissure.

Animals↗
PubMed2006

Neural crest and the development of the enteric nervous system.

The formation of the enteric nervous system (ENS) is a particularly interesting example of the migratory ability of the neural crest and of the complexity of structures to which neural crest cells contribute. The distance that neural crest cells migrate to colonize the entire length of the gastrointestinal tract exceeds that of any other neural crest cell population. Furthermore, this migration takes a long time--over 25% of the gestation period for mice and around 3 weeks in humans. After colonizing the gut, neural crest-derived cells within the gut wall then differentiate into glial cells plus many different types of neurons, and generate the most complex part of the peripheral nervous system.

Animals↗
PubMed2006

The cell adhesion molecule l1 is required for chain migration of neural crest cells in the developing mouse gut.

BACKGROUND & AIMS: During development, the enteric nervous system is derived from neural crest cells that emigrate from the hindbrain, enter the foregut, and colonize the gut. Defects in neural crest migration can result in intestinal aganglionosis. Hirschsprung's disease (congenital aganglionosis) is a human condition in which enteric neurons are absent from the distal bowel. A number of clinical studies have implicated the cell adhesion molecule L1 in Hirschsprung's disease. We examined the role of L1 in the migration of neural crest cells through the developing mouse gut. METHODS: A variety of in vitro and in vivo assays were used to examine: (1) the effect of L1 blocking antibodies or exogenous soluble L1 protein known to compromise L1 function on the rate of crest cell migration, (2) the effect of blocking L1 activity on the dynamic behavior of crest cells using time-lapse microscopy, and (3) whether the colonization of the gut by crest cells in L1-deficient mice differs from control mice. RESULTS: We show that L1 is expressed by neural crest cells as they colonize the gut. Perturbation studies show that disrupting L1 activity retards neural crest migration and increases the number of solitary neural crest cells. L1-deficient mice show a small but significant reduction in neural crest cell migration at early developmental stages, but the entire gastrointestinal tract is colonized. CONCLUSIONS: L1 is important for the migration of neural crest cells through the developing gut and is likely to be involved in the etiology of Hirschsprung's disease.

Animals↗
PubMed2005

Sample size and the detection of correlation--a signal detection account: comment on Kareev (2000) and Juslin and Olsson (2005).

Simulations examined the hypothesis that small samples can provide better grounds for inferring the existence of a population correlation, p, than can large samples. Samples of 5, 7, 10, 15, or 30 data pairs were drawn either from a population with p=0 or from one with p>0. When decision accuracy was assessed independently for each level of the decision criterion, there was a criterion-specific small-sample advantage. For liberal criteria, accuracy was greater for large than for small samples, but for conservative criteria, the opposite result occurred. There was no small-sample advantage when accuracy was measured as the area under a receiver operating characteristic curve or as the posterior probability of a hit. The results show that small-sample advantages can occur, but under limited conditions.

Humans↗
PubMed2003

Characterization of lacZ-expressing cells in the gut of embryonic and adult DbetaH-nlacZ mice.

In mice that express lacZ under the control of a human dopamine beta-hydroxylase gene promoter (DbetaH-nlacZ mice), the nuclei of enteric neurons express the transgene, as shown by the presence of beta-galactosidase (beta-gal) staining (Mercer et al. [1991] Neuron 7:703-716). The transgene is also expressed by neural crest-derived cells in the developing gut before their differentiation into neurons or glial cells (Kapur et al. [1992] Development 116:167-175). However, the cell types expressing the DbetaH-nlacZ transgene within the developing and adult gut have not been fully characterized. Whole-mount preparations of embryonic and adult gut were processed for histochemistry or immunohistochemistry to reveal beta-gal plus markers of undifferentiated neural crest cells (in embryos) or enteric neurons (in adults). In embryonic mice, over 90% of undifferentiated neural crest-derived cells (identified using antibodies to p75) were beta-gal(+). Importantly, crest-derived cells at the migratory wavefront were all beta-gal(+). In adult mice, only a subpopulation of enteric neurons was beta-gal(+), while glial cells showed no beta-gal staining. Considerable variation was observed between the small intestine and colon in the proportion of myenteric neurons that showed beta-gal staining. We examined whether known classes of enteric neurons varied in their expression of DbetaH-nlacZ. In the myenteric plexus of the jejunum and colon, large calretinin(+) neurons did not express lacZ, suggesting that the incomplete penetrance of the DbetaH-nlacZ transgene observed in adult mice is not random. We conclude that the DbetaH-nlacZ transgene provides a reliable marker for examining the colonization of the developing gut by neural crest cells. However, in adult mice, there is variation between mice, between gut regions, and between different classes of enteric neurons in the expression of the transgene.

Animals↗
PubMed2002

Chondroitin sulfate disrupts axon pathfinding in the optic tract and alters growth cone dynamics.

Little is known about the cues that guide retinal axons across the diencephalon en route to their midbrain target, the optic tectum. Here we show that chondroitin sulfate proteoglycans are differentially expressed within the diencephalon at a time when retinal axons are growing within the optic tract. Using exposed brain preparations, we show that the addition of exogenous chondroitin sulfate results in retinal pathfinding errors. Retinal axons disperse widely from their normal trajectory within the optic tract and extend aberrantly into inappropriate regions of the forebrain. Time-lapse analysis of retinal growth cone dynamics in vivo shows that addition of exogenous chondroitin sulfate causes intermittent stalling and increases growth cone complexity. These results suggest that chondroitin sulfate may modulate the guidance of retinal axons as they grow through the diencephalon towards the optic tectum.

Animals↗
PubMed2002

Expression of UNC-5 in the developing Xenopus visual system.

Netrin-1 and its receptors deleted in colorectal cancer (DCC) and neogenin are expressed within the developing visual system and have been implicated in mediating axon guidance and cell migration. However, the expression of the netrin-1 receptor UNC-5 has not yet been addressed. Here we clone Xenopus UNC-5 (XUNC-5) and describe its expression within the developing visual system. Xunc-5 transcripts are expressed within the developing optic vesicles and later become restricted to the dorsal ciliary marginal zone, a site of retinoblast proliferation and differentiation. This highly restricted expression pattern could make XUNC-5 an excellent marker of dorsal retinal precursor cells.

Amino Acid Sequence↗