Molecular investigations of development and diseases of the brain of higher mammals using the ferret

Abstract

The brains of higher mammals such as primates and carnivores contain well-developed unique brain structures. Uncovering the physiological functions, developmental mechanisms and evolution of these brain structures would greatly facilitate our understanding of the human brain and its diseases. Although the anatomical and electrophysiological features of these brain structures have been intensively investigated, our knowledge about their molecular bases is still limited. To overcome this limitation, genetic techniques for the brains of carnivores and primates have been established, and molecules whose expression patterns correspond to these brain structures were identified recently. To investigate the functional roles of these molecules, rapid and efficient genetic manipulation methods for higher mammals have been explored. In this review, recent advances in molecular investigations of the brains of higher mammals are discussed, mainly focusing on ferrets (Mustela putorius furo).

Keywords: cerebral cortex; ferret; gyrus; in utero electroporation; outer subventricular zone.

Figure 1.

The ferret and its brain. (A) An adult ferret. The ferret has an average length of about 50 cm and weight of about 1–2 kg. (B) A dorsal view of the ferret brain. The cortical gyri and sulci are clearly present. Scale bar, 1 cm. (Adapted from Kawasaki et al., 2012)²¹⁾

Figure 2.

GFP in the ferret brain expressed using in utero electroporation. Scale bars, 1 cm. (Adapted from Kawasaki et al., 2012)²¹⁾

Figure 3.

The brain of TD ferrets. (A) A dorsal view of the TD ferret brain. FGF8 was electroporated into the right cortex. (B) A coronal section of the cerebral cortex of TD ferrets stained with Hoechst 33342. Note that additional sulci (asterisks) and gyri with normal layer structures were formed by expressing FGF8. Scale bars, 4 mm (A), 6 mm (B). (Adapted from Masuda et al., 2015)⁵²⁾

Figure 4.

IFL-like fibers in the developing ferret cerebral cortex. When GFP was expressed in layer 2/3 neurons using in utero electroporation, GFP-positive fibers were observed in the inner OSVZ (arrows). Low magnification images (upper panels) and high magnification images (lower panels) are shown. CP, cortical plate. Scale bars, 500 µm (upper) and 200 µm (lower). (Adapted from Kawasaki et al., 2013)²²⁾

Figure 5.

Two hypotheses about the relationship between M and P cells in primates and Y and X cells in carnivores. The expression pattern of FoxP2 is consistent with hypothesis 1.