A role forfoxd3andsox10in the differentiation of gonadotropin-releasing hormone (GnRH) cells in the zebrafishDanio rerio

Abstract

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.

Developing a sense of scents: Plasticity in olfactory placode formation

“…Consistent with this hypothesis, we have found that in zebrafish GnRH3 cells of the terminal nerve and GnRH2 cells of the midbrain (Fig. 2B,C) have their origin in the cranial neural crest [53,57,60] whereas the GnRH cells of the hypothalamus arise from the region of the adenohypophyseal placode [54,56,57,60] (Fig. 2D).…”

“…The greatest effect observed to date in the "knockdown" of gene function is the loss or reduction of endocrine GnRH (hypothalamic) cells in animals deficit in kal1a protein. Strikingly there was had no effect on neuromodulatory midbrain or nervus terminalis GnRH cells [57]. The olfactory nerves of these animals were disrupted but not absent.…”

“…In contrast, migratory route of cranial neural crest cells passing dorsal to the eye and populating the frontal mass is not well understood. Using a transgenic sox10-GFP line of zebrafish [48] (GFP expressed in the neural crest) we characterized the development of cranial neural crest cells to determine whether there was any cell mixing of olfactory placodes and cranial neural crest during formation of the olfactory sensory system [17,57]. At approximately 13 hours post-fertilization (6-8 somites), the neural crest cells migrate anteriorly as a group and separate at the anterior end of the neural tube.…”

“…Given the incomplete nature of the zebrafish genome this is not particularly surprising. The differential expression of GnRH in situ probes (GnRH2, GnRH3) and immunocytochemical labeling with antibodies recognizing GnRH1 in mammals or multiple forms of GnRH suggests that zebrafish like other many fishes may have a third form of GnRH [47,57]. Thus, analysis in chick and fish indicates that the GnRH cells arise from the border of the neural plate suggesting that the neural ridge has the potential to generate GnRH cells across vertebrates [54].…”

Anosmin-1a is required for fasciculation and terminal targeting of olfactory sensory neuron axons in the zebrafish olfactory system

“…Previous studies demonstrated that though the kal1a gene played an essential role in several developmental processes in zebrafish embryos, including GnRH neuron migration (Whitlock et al, 2005), the journey of the posterior lateral line primordium and OS development (the present study), none of these processes were defective following anosmin-1b depletion (Whitlock et al, 2005;Yanicostas et al, 2008; data not shown). Therefore, we focused our investigations on the function of anosmin-1a in OS development.…”