Biomedical subjects

Kathleen E Whitlock

Publications and source records attributed to Kathleen E Whitlock.

5 recordsLinked to original sources

PubMed2005

A role for foxd3 and sox10 in the differentiation of gonadotropin-releasing hormone (GnRH) cells in the zebrafish Danio rerio.

Gonadotropin-releasing hormone (GnRH) is found in a wide range of vertebrate tissues, including the nervous system. In general, GnRH has two functions: endocrine, acting as a releasing hormone; and neuromodulatory, affecting neural activity in the peripheral and central nervous system. The best understood population of GnRH cells is that of the hypothalamus, which is essential for reproduction. Less well understood are the populations of GnRH cells found in the terminal nerve and midbrain, which appear to be neuromodulatory in function. The GnRH-containing cells of the midbrain are proposed to arise from the mesencephalic region of the neural tube. Previously, we showed that neuromodulatory GnRH cells of the terminal nerve arise from cranial neural crest. To test the hypothesis that neuromodulatory GnRH cells of the midbrain also arise from neural crest, we used gene knockdown experiments in zebrafish to disrupt neural crest development. We demonstrate that decrement of the function of foxd3 and/or sox10, two genes important for the development and specification of neural crest, resulted in a reduction and/or loss of GnRH cells of the midbrain, as well as a reduction in the number of terminal nerve GnRH cells. Therefore, our data support a neural crest origin for midbrain GnRH cells. Additionally, we demonstrate that knockdown of kallmann gene function resulted in the loss of endocrine GnRH cells of the hypothalamus, but not of neuromodulatory GnRH cells of the midbrain and terminal nerve, thus providing additional evidence for separate pathways controlling the development of neuromodulatory and endocrine GnRH cells.

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PubMed2004

Development of the nervus terminalis: origin and migration.

The origin of the nervus terminalis is one of the least well understood developmental events involved in generating the cranial ganglia of the forebrain in vertebrate animals. This cranial nerve forms at the formidable interface of the anteriormost limits of migrating cranial neural crest cells, the terminal end of the neural tube and the differentiating olfactory and adenohypophyseal placodes. The complex cellular interactions that give rise to the various structures associated with the sensory placode (olfactory) and endocrine placode (adenohypophysis) surround and engulf this enigmatic cranial nerve. The tortured history of nervus terminalis development (see von Bartheld, this issue, pages 13-24) reflects the lack of consensus on the origin (or origins), as well as the experimental difficulties in uncovering the origin, of the nervus terminalis. Recent technical advances have allowed us to make headway in understanding the origin(s) of this nerve. The emergence of the externally fertilized zebrafish embryo as a model system for developmental biology and genetics has shed new light on this century-old problem. Coupled with new developmental models are techniques that allow us to trace lineage, visualize gene expression, and genetically ablate cells, adding to our experimental tools with which to follow up on studies provided by our scientific predecessors. Through these techniques, a picture is emerging in which the origin of at least a subset of the nervus terminalis cells lies in the cranial neural crest. In this review, the data surrounding this finding will be discussed in light of recent findings on neural crest and placode origins.

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PubMed2004

Temporal and spatial expression of gonadotropin releasing hormone (GnRH) in the brain of developing zebrafish (Danio rerio).

Gonadotropin releasing hormone (GnRH) is a neuroendocrine decapeptide found in all vertebrate animals. The best understood function of GnRH is its endocrine function as a releasing hormone acting on the pituitary. But GnRH also functions as a neuromodulator within the nervous system. In a given species, GnRH occurs in a variety of forms that fall into three general categories based on pattern of protein/gene expression in the brain and amino acid sequence. The salmon GnRH (sGnRH), is found in the terminal nerve, where it has a neuromodulatory function. The sGnRH form is also the hypothalamic form in many fishes, although some fishes have a species specific form in the hypothalamus. Finally, chicken-GnRH-II (cGnRH-II), the most highly conserved form, is found in the midbrain where its function remains unclear. Here we have cloned the sGnRH and cGnRH-II cDNAs from zebrafish. By conducting stage specific in situ hybridization in developing zebrafish embryos, we provide a description of the spatial and temporal expression patterns of these genes. The location of sGnRH and cGnRH-II expressing cells is in agreement with previous reports of GnRH in the brains of adult fishes. Our results provide the first developmental description of GnRH gene expression where cGnRH-II and sGnRH are initially expressed at the onset of the first day after fertilization. Unlike what has been reported in many adult fishes, we did not find sGnRH expressed in the hypothalamic population during development.

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PubMed2004

A new model for olfactory placode development.

The peripheral nervous system of vertebrate animals arises primarily from the interaction of cranial neural crest and sensory placodes. Placodes are described as thickenings of ectoderm that arise through cell division during neural tube formation. The olfactory sensory system is one component of the peripheral nervous system that arises from paired sensory placodes during development. The olfactory placodes give rise to the primary sensory neurons, support cells and basal cells of the olfactory epithelium. Recent evidence from work in zebrafish and chick suggests that the olfactory and auditory placodes arise from large fields of cells that converge to form the sensory placode. The olfactory placodes arise from within the neural plate, and cell division is apparent only after the sensory placodes are morphologically distinct. As the olfactory placode is forming, its precursors must segregate from their neighboring fields which will give rise to the adenohypophyseal placode, cranial neural crest, and telencephalon. Analysis has shown that the endocrine cells thought to arise from the olfactory placode originate in the neighboring adenohypophyseal and cranial neural crest domains. The borders separating the domains are plastic, where cells sort as they move, and cell fate is dependent on the identity of neighbors once the cells have converged to form the sensory placode. Thus there is degeneracy built into the system such that cells accommodate changes in the environment until cell migrations controlling the formation of the sensory placodes are complete.

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PubMedDate not supplied

Origin and development of GnRH neurons.

Gonadotropin-releasing hormone (GnRH) is an essential decapeptide, with both endocrine and neuromodulatory functions in vertebrates. GnRH-containing cells of the forebrain were thought to originate in the olfactory placode and migrate to their central nervous system destinations, and those of the midbrain to arise locally from the neural tube. Here, the embryonic origins of GnRH cells are re-examined in light of recent data suggesting that forebrain GnRH cells arise from the anterior pituitary placode and cranial neural crest, from where they migrate to their final destinations. The emerging picture suggests that GnRH cells do not originate from the olfactory placodes, but arise from multiple embryonic origins, and transiently associate with the developing olfactory system as they migrate to ventral forebrain locations.

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