The role of neurotrophins during early development

Abstract

The effects of neurotrophins during the middle and late stages of development are well known. It was previously thought that neurotrophins had no role during early development, but this is not the case and is the subject of this review article. The earliest neurotrophin receptor expressed is that for neurotrophin-3 (NT-3). TrkC is detected in the neural plate and is present in the neural tube. Initially, the distribution of TrkC is homogenous, but it becomes localized to specific regions of the neural tube as the neural tube differentiates. The receptor for brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5), TrkB, is detected somewhat later than TrkC in the neural tube where it is also differentially localized. In contrast, the NGF receptor, TrkA, was not detected during early development. Both NT-3 and BDNF have been shown to have effects in vitro during early development. NT-3 caused an increase in neurite outgrowth and apoptosis in neural plate explants, and promoted differentiation of progenitors into motoneurons. BDNF increased the number of motoneurons in neural tube explants. These data suggest that NT-3 and BDNF may play a role during early development in vivo.

Figure 1

Rostro-caudal expression of trkC mRNA in the chicken embryo. At stage 4 (A), trkC mRNA expression (indicated by red) is limited to the anterior portion of the neural plate (NP); there is no staining of the primitive streak (PS) or notochordal process (N). trkC mRNA is found along the length of the forming neural tube (NT) at stage 8 (B), while at stage 11 (C) it becomes restricted to the anterior prosencephalon, the hindbrain (except for rhombomeres 1 and 4), and the remainder of the neural tube adjacent to somites. By stage 15 (D), trkC mRNA is only detected in rhombomeres 3 and 5.

Figure 2

Cross-sectional expression of trkC mRNA and NT-3-like immunoreactivity in the chicken embryo. At stage 9 (A), trkC mRNA expression (indicated by red) is located throughout the forming neural tube (NT) with the exception of the midline; there is no staining of the ectoderm (E) or notochord (N). From stages 11 through 14 (B), trkC mRNA expression is higher in the dorsal neural tube while at stage 18 (C) it is expressed in the peripheral (mantle) layer. At stages 13 (D) and 19 (E), NT-3-like immunoreactivity (indicated by blue) is located throughout the forming neural tube.

Figure 3

Cross-sectional expression of trkB and BDNF mRNA in the chicken embryo. At stage 10 (A), trkB mRNA expression (indicated by red) is located in the ventral region of the neural tube (NT) with the exception of the floor plate; there is no mRNA detected in the ectoderm (E) or notochord (N). Its localization becomes more restricted by stage 12 (B) and is limited to the ventricular zone by stage 16 (C). At stages 13 (D) and 19 (E), BDNF mRNA (indicated by blue) is limited to the dorsal part of the neural tube with the exception of the dorsal-most region.