Brain‐derived neurotrophic factor and TrkB tyrosine kinase receptor gene expression in zebrafish embryo and larva

Abstract

The genes that encode the neurotrophin family of secreted polypeptides and the Trk family of high affinity neurotrophin transmembrane protein tyrosine kinase receptors are induced at the time of neurogenesis in mammals and are known to play critical roles in nervous system development. We show here that in contrast to mammals, the genes encoding the neurotrophin brain-derived neurotrophic factor (BDNF) and the neurotrophin receptor TrkB are expressed throughout embryonic development in the zebrafish. At the embryonic stages preceding transcription of endogenous genes all cells contain BDNF transcripts and immunoreactive BDNF and the trkB transcripts lack the region that encodes a kinase domain. As development proceeds, progressively fewer cells contain BDNF transcripts and by the time of neurogenesis the trkB transcripts encode a kinase-domain. In the 4-day-old larva, a small subset of specialized sensory cells on the surface and cells in deeper structures including the gill arches, fin, and cloaca express the BDNF gene at high levels in a promoter-specific fashion. This progressive restriction of BDNF gene expression must involve an extinction of BDNF gene transcription in some and induction of high levels of transcription in a promoter-specific fashion in other cells.

Decreased BDNF Levels Are a Major Contributor to the Embryonic Phenotype of Huntingtin Knockdown Zebrafish

“…early stages and in cells lining the gill arches and the jaw cartilages at 4 dpf (Lum et al, 2001). Our data show that BDNF is critical for normal development of the cartilage in the mandibular, hyoid and branchial arches.…”

“…1, available at www.jneurosci.org as supplemental material). However, as described previously by Lum et al (2001), the detection of mature BDNF was much weaker, so it was not feasible to reliably quantify this band.…”

“…The mAB248 was made against recombinant human BDNF aa129 -247 and recognizes both mature and pro-BDNF. As described before (Lum et al, 2001), detection of mature BDNF was much weaker than for pro-BDNF which is why this isoform was used to quantify BDNF levels. Immunosignals were visualized with HRP-coupled anti-mouse antibody and ECL substrate (GE Healthcare).…”

Brain-Derived Neurotrophic Factor mRNA Expression in the Brain of the Teleost Fish, <i>Anguilla anguilla,</i> the European Eel

“…It is important dur- [Theiss and Güntürkün, 2001] and frog [Duprey-Díaz et al, 2002] tectum and in the hypothalamo-hypophyseal system of Xenopus [Wang et al, 2005]. With regard to teleost fish, BDNF expression has been confirmed in the brain of the southern platyfish [Götz et al, 1992], in the developing zebrafish brain and retina [Hashimoto and Heinrich, 1997;Lum et al, 2001], and in the tench retina [Caminos et al, 1999]. Five neurotrophin receptors have been described in zebrafish [Martin et al, 1995], two of which have been reported to be isoforms of the Trk B receptor and their mRNA is widely distributed throughout the brain and spinal cord of larval zebrafish [Martin et al, 1995].…”

Conservation and Early Expression of Zebrafish Tyrosine Kinases Support the Utility of Zebrafish as a Model for Tyrosine Kinase Biology

“…[22][23][24][25] The nonreceptor tyrosine kinase SRC is involved in egg activation during fertilization, 26 and FAK has a role in cell adhesion and exhibits noncanonical regulatory phosphorylation. 27,28 The MET receptor tyrosine kinase regulates liver and cerebellum development; [29][30][31] the TEC tyrosine kinase is expressed in the zebrafish kidney; 32 the TRKB receptor tyrosine kinase is expressed throughout embryonic development and lacks a kinase domain until neurogenesis; 33 MuSK functions in neuromuscular synapse formation; 34 and PTK7 knockdown results in convergent extension defects. 35 The zebrafish cardiovascular system is profoundly influenced by tyrosine kinases.…”