The Ferret as a Model System for Neocortex Development and Evolution

Carlotta Gilardi,Nereo Kalebic

doi:10.3389/fcell.2021.661759

Carlotta Gilardi, Nereo Kalebic

Open Access

https://doi.org/10.3389/fcell.2021.661759

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Abstract

The neocortex is the largest part of the cerebral cortex and a key structure involved in human behavior and cognition. Comparison of neocortex development across mammals reveals that the proliferative capacity of neural stem and progenitor cells and the length of the neurogenic period are essential for regulating neocortex size and complexity, which in turn are thought to be instrumental for the increased cognitive abilities in humans. The domesticated ferret, Mustela putorius furo, is an important animal model in neurodevelopment for its complex postnatal cortical folding, its long period of forebrain development and its accessibility to genetic manipulation in vivo. Here, we discuss the molecular, cellular, and histological features that make this small gyrencephalic carnivore a suitable animal model to study the physiological and pathological mechanisms for the development of an expanded neocortex. We particularly focus on the mechanisms of neural stem cell proliferation, neuronal differentiation, cortical folding, visual system development, and neurodevelopmental pathologies. We further discuss the technological advances that have enabled the genetic manipulation of the ferret in vivo. Finally, we compare the features of neocortex development in the ferret with those of other model organisms.

Highlights

The ferret (Mustela putorius furo) is a small carnivore, domesticated more than 2000 years ago (Davison et al, 1999)
The ferret is characterized by an expanded and folded neocortex and a diversity of proliferative neural stem and progenitor cells (Kawasaki, 2014; Fernandez et al, 2016; Kalebic et al, 2019). These features are generally accepted to be fundamental for the evolutionary expansion of the neocortex, which in turn is considered to underlie the increased cognitive abilities of humans (Rakic, 2009; Dehay et al, 2015; Fernandez et al, 2016; Sousa et al, 2017; Kalebic and Huttner, 2020)
The ferret is used as an animal model to study the evolutionary expansion of the neocortex and those aspects of human brain development that cannot be modeled in organisms with a small brain, such as rodents

Summary

INTRODUCTION

The ferret (Mustela putorius furo) is a small carnivore, domesticated more than 2000 years ago (Davison et al, 1999). In this review we discuss those features of the ferret neurodevelopment that make this animal an important model system for the study of cell biology of neural progenitors, neuronal differentiation and migration, mechanisms underlying gyrification, development of the sensory systems and human pathologies pertinent to the central nervous system. The ferret contains all the histological and cell biological features required to build an expanded neocortex (Figure 1) It has a thick SVZ which splits into the iSVZ and oSVZ at E33 (Reillo and Borrell, 2012; Martinez-Martinez et al, 2016). This model was generated by subjecting the ferret kits to sub-lethal, chronic hypoxia from P10 to P20, which increased astrocytosis and decreased myelination, similar to human patients (Tao et al, 2012)

DISCUSSION

CONCLUSION