The Development and Evolution
8 of the Vertebrate Neural Crest
Insights from Xenopus
Joshua R. York and Carole LaBonne
CONTENTS
8.1. Introduction ................................................................................................................................................................ 125
8.2. Historical Background: The Importance of Amphibian Models in Early Neural Crest Research ............................. 126
8.3. Insights into Neural Crest Development from Xenopus in the Era of Molecular Biology and “-Omics” ................. 127
8.3.1. Neural Crest Progenitors and Establishment of the Neural Plate Border ..................................................... 127
8.3.2. Neural Crest EMT and Migration ................................................................................................................. 129
8.3.3. Neural Crest Lineage Diversif cation ............................................................................................................ 131
8.4. The Origins of Neural Crest Potential........................................................................................................................ 131
8.5. Future Directions and Outlook ................................................................................................................................... 133
References ............................................................................................................................................................................ 134
8.1. INTRODUCTION
The frst vertebrates appeared some 500 million years
ago, and much of what fueled their origin and early
diversifcation can be credited to a small population of
stem cells that appear only transiently during embryonic
development—the neural crest (Gans and Northcutt 1983;
Hall 2018; York and McCauley 2020a, 2020b; Trainor
2013). Neural crest cells are centrally important to vertebrates because they are responsible for generating many
of the morphological, physiological, and behavioral traits
that defne the vertebrate clade. Among these are cartilage
and bone elements of the head, face, and neck; nearly all
of the sensory neurons and glia of the peripheral nervous
system; colorful patterns of pigmentation in skin, feathers,
and scales; and even parts of the heart and teeth (Green et
al. 2015; Jandzik et al. 2015; Square et al. 2016; Martik,
Gandhi et al. 2019).
Neural crest cells are found in all vertebrate embryos, and
their development follows a course of events that is roughly
similar across even distantly related groups ( Green et al. 2015 ;
York and McCauley 2020a ). The precursors of these cells arise
at the lateral edges of the neural plate (presumptive central nervous system, or CNS), a region known as the neural plate border
( Le Douarin and Kalcheim 1999 ; Hall 2008a). During neurulation, neural crest stem cells expressing a defnitive set of generegulatory factors localize to the dorsal region (“crest”) of the
closing neural tube. From there, they undergo an epitheliumto-mesenchyme transition (EMT), delaminate from the neural
epithelium, and migrate extensively throughout the embryo
to sites where they will give rise to both ectomesenchymal
(cartilage, bone, smooth muscle) and non-ectomesenchymal
(neurons, glia, pigment) derivatives ( Le Douarin and Kalcheim
1999 ; Hall 2008a , 2008b ). By studying and comparing how
these processes play out in different vertebrates, it is possible
to build a comprehensive picture of a shared developmental
program for neural crest development.
Much of our knowledge of neural crest developmental
mechanisms has come from studies in a handful of vertebrate organisms, including mouse, chicken, zebraf sh,
and amphibians. These so-called model systems are the
workhorses of modern embryology research, and for good
reason. The embryos are relatively easy to obtain and rear
in simple laboratory settings, they have well-annotated
genomes and transcriptomes, and they are amenable to
a wide range of molecular-genetic techniques. Among
these, amphibian embryos—particularly those of the
genus Xenopus—have historically been a “go-to” for scientists using perturbation experiments to gain mechanistic
insights into developmental processes ( Elsdale et al. 1960 ;
Akira and Ide 1987 ; Sadaghiani and Thiébaud 1987 ). With
the advent of powerful molecular biology and genomics
approaches ( Vize and Zorn 2017 ; Blum and Ott 2018 ;
Kakebeen and Wills 2019 ), the contributions from this
model system have only continued to grow. Indeed, studies of the neural crest in Xenopus and other amphibians
have yielded important discoveries regarding the developmental and evolutionary origins of these stem cells, their
role in sculpting the vertebrate body plan and producing
evolutionary novelty, and their links to human congenital
disorders and diseases ( Piekarski et al. 2014 ; LaBonne and
Zorn 2015 ; Greenberg et al. 2019 ).
DOI: 10.1201/9781003050230-9
125
8 of the Vertebrate Neural Crest
Insights from Xenopus
Joshua R. York and Carole LaBonne
CONTENTS
8.1. Introduction ................................................................................................................................................................ 125
8.2. Historical Background: The Importance of Amphibian Models in Early Neural Crest Research ............................. 126
8.3. Insights into Neural Crest Development from Xenopus in the Era of Molecular Biology and “-Omics” ................. 127
8.3.1. Neural Crest Progenitors and Establishment of the Neural Plate Border ..................................................... 127
8.3.2. Neural Crest EMT and Migration ................................................................................................................. 129
8.3.3. Neural Crest Lineage Diversif cation ............................................................................................................ 131
8.4. The Origins of Neural Crest Potential........................................................................................................................ 131
8.5. Future Directions and Outlook ................................................................................................................................... 133
References ............................................................................................................................................................................ 134
8.1. INTRODUCTION
The frst vertebrates appeared some 500 million years
ago, and much of what fueled their origin and early
diversifcation can be credited to a small population of
stem cells that appear only transiently during embryonic
development—the neural crest (Gans and Northcutt 1983;
Hall 2018; York and McCauley 2020a, 2020b; Trainor
2013). Neural crest cells are centrally important to vertebrates because they are responsible for generating many
of the morphological, physiological, and behavioral traits
that defne the vertebrate clade. Among these are cartilage
and bone elements of the head, face, and neck; nearly all
of the sensory neurons and glia of the peripheral nervous
system; colorful patterns of pigmentation in skin, feathers,
and scales; and even parts of the heart and teeth (Green et
al. 2015; Jandzik et al. 2015; Square et al. 2016; Martik,
Gandhi et al. 2019).
Neural crest cells are found in all vertebrate embryos, and
their development follows a course of events that is roughly
similar across even distantly related groups ( Green et al. 2015 ;
York and McCauley 2020a ). The precursors of these cells arise
at the lateral edges of the neural plate (presumptive central nervous system, or CNS), a region known as the neural plate border
( Le Douarin and Kalcheim 1999 ; Hall 2008a). During neurulation, neural crest stem cells expressing a defnitive set of generegulatory factors localize to the dorsal region (“crest”) of the
closing neural tube. From there, they undergo an epitheliumto-mesenchyme transition (EMT), delaminate from the neural
epithelium, and migrate extensively throughout the embryo
to sites where they will give rise to both ectomesenchymal
(cartilage, bone, smooth muscle) and non-ectomesenchymal
(neurons, glia, pigment) derivatives ( Le Douarin and Kalcheim
1999 ; Hall 2008a , 2008b ). By studying and comparing how
these processes play out in different vertebrates, it is possible
to build a comprehensive picture of a shared developmental
program for neural crest development.
Much of our knowledge of neural crest developmental
mechanisms has come from studies in a handful of vertebrate organisms, including mouse, chicken, zebraf sh,
and amphibians. These so-called model systems are the
workhorses of modern embryology research, and for good
reason. The embryos are relatively easy to obtain and rear
in simple laboratory settings, they have well-annotated
genomes and transcriptomes, and they are amenable to
a wide range of molecular-genetic techniques. Among
these, amphibian embryos—particularly those of the
genus Xenopus—have historically been a “go-to” for scientists using perturbation experiments to gain mechanistic
insights into developmental processes ( Elsdale et al. 1960 ;
Akira and Ide 1987 ; Sadaghiani and Thiébaud 1987 ). With
the advent of powerful molecular biology and genomics
approaches ( Vize and Zorn 2017 ; Blum and Ott 2018 ;
Kakebeen and Wills 2019 ), the contributions from this
model system have only continued to grow. Indeed, studies of the neural crest in Xenopus and other amphibians
have yielded important discoveries regarding the developmental and evolutionary origins of these stem cells, their
role in sculpting the vertebrate body plan and producing
evolutionary novelty, and their links to human congenital
disorders and diseases ( Piekarski et al. 2014 ; LaBonne and
Zorn 2015 ; Greenberg et al. 2019 ).
DOI: 10.1201/9781003050230-9
125