Signaling Pathways in Anterior5 Posterior Patterning
Chenbei Chang
CONTENTS
5.1. Introduction .................................................................................................................................................................. 51
5.2. Classical Experimental Embryology Studies Brought Forth Different Models on Anterior-Posterior
Neural Patterning ......................................................................................................................................................... 51
5.3. Insight into Signaling Pathways Controlling Anterior-Posterior Embryonic Patterning from Molecular
Biological Studies ........................................................................................................................................................ 54
5.3.1. Retinoic Acid Signaling .................................................................................................................................. 54
5.3.2. Fibroblast Growth Factor Signaling ................................................................................................................ 55
5.3.3. Wnt/β-Catenin Signaling Pathway .................................................................................................................. 56
5.3.4. Multiple Pathways and Signal Integration ...................................................................................................... 57
5.4. Synthesis of the Classical and Modern Studies and Some Unresolved Issues ............................................................ 58
Acknowledgments .................................................................................................................................................................. 60
References .............................................................................................................................................................................. 60
5.1. INTRODUCTION
The work of Hans Spemann and Hilde Mangold on induction
of a secondary dorsal axis by a piece of transplanted dorsal
marginal tissue was one of the most impactful in the f eld of
embryology ( Spemann and Mangold, 1924 ; Spemann and
Mangold, 2001 ). The experiments demonstrated not only
developmental plasticity of early amphibian embryos but
also the phenomenon of cell fate re-specifcation in response
to inductive tissue interactions, which provide strong support for cell-cell communication based on the “organizer”
idea (reviewed in Chapter 4 ). In the same work, Spemann
and Mangold also noted that the anterior portion of the
secondary neural tube and the optic vesicles were missing. They discussed the possibility of defciency in certain
parts of the implanted organizer that would be necessary
for the induction of anterior neural plate with eye primordia ( Spemann and Mangold, 1924 ; Spemann and Mangold,
2001 ). The issue of the organizer with regionalized headand trunk-inducing ability was further taken up by Spemann
in later experiments that used dorsal lips from early or older
gastrula embryos, which showed that early organizers could
induce a full secondary axis, including a head, whereas older
organizers induced a partial ectopic axis with only trunk and
tail regions ( Hamburger, 1988 ; Spemann, 1936 ). Hence, it
was understood early on that neural induction and specif cation of regional characteristics (patterning) of the induced
neural tissues (head or trunk) were interlinked processes,
and the source of the inducers, the timing of induction, and
the properties of the responding tissues might all inf uence
the outcome. The issue of patterned neural induction along
the embryonic axis was actively pursued in subsequent
studies. Spemann’s students as well as scientists from other
institutions investigated inductive interactions that gave
rise to distinct brain structures or spinal cord, and different
models were put forward to account for the signals involved
in the process ( Doniach, 1993 ; Slack and Tannahill, 1992 ).
In the absence of the identities of the inducing substances,
the quest for the anterior (cranial) and posterior (trunk and
tail) neural inducers persisted to modern days. The advent
of technologies for examining gene expression and manipulating gene functions in recent decades greatly enhanced
our ability to interrogate this classical question with new
rigor, and important insights have been gained into molecular control of both neural induction and neural patterning.
This is especially pertinent using Xenopus, currently the
most popular amphibian model of early development. This
chapter aims to review key aspects of classical works that
inspired different models on anterior-posterior (AP) neural
patterning and discuss several signaling pathways identif ed
using molecular biology approaches that regulate AP neural specifcation. Considerations on a number of remaining
issues regarding AP patterning are also discussed brief y.
5.2. CLASSICAL EXPERIMENTAL EMBRYOLOGY
STUDIES BROUGHT FORTH
DIFFERENT MODELS ON ANTERIORPOSTERIOR NEURAL PATTERNING
Development of structures along the head-to-tail (a.k.a.
anterior-posterior or rostral-caudal) axis in vertebrate
DOI: 10.1201/9781003050230-6
51
Chenbei Chang
CONTENTS
5.1. Introduction .................................................................................................................................................................. 51
5.2. Classical Experimental Embryology Studies Brought Forth Different Models on Anterior-Posterior
Neural Patterning ......................................................................................................................................................... 51
5.3. Insight into Signaling Pathways Controlling Anterior-Posterior Embryonic Patterning from Molecular
Biological Studies ........................................................................................................................................................ 54
5.3.1. Retinoic Acid Signaling .................................................................................................................................. 54
5.3.2. Fibroblast Growth Factor Signaling ................................................................................................................ 55
5.3.3. Wnt/β-Catenin Signaling Pathway .................................................................................................................. 56
5.3.4. Multiple Pathways and Signal Integration ...................................................................................................... 57
5.4. Synthesis of the Classical and Modern Studies and Some Unresolved Issues ............................................................ 58
Acknowledgments .................................................................................................................................................................. 60
References .............................................................................................................................................................................. 60
5.1. INTRODUCTION
The work of Hans Spemann and Hilde Mangold on induction
of a secondary dorsal axis by a piece of transplanted dorsal
marginal tissue was one of the most impactful in the f eld of
embryology ( Spemann and Mangold, 1924 ; Spemann and
Mangold, 2001 ). The experiments demonstrated not only
developmental plasticity of early amphibian embryos but
also the phenomenon of cell fate re-specifcation in response
to inductive tissue interactions, which provide strong support for cell-cell communication based on the “organizer”
idea (reviewed in Chapter 4 ). In the same work, Spemann
and Mangold also noted that the anterior portion of the
secondary neural tube and the optic vesicles were missing. They discussed the possibility of defciency in certain
parts of the implanted organizer that would be necessary
for the induction of anterior neural plate with eye primordia ( Spemann and Mangold, 1924 ; Spemann and Mangold,
2001 ). The issue of the organizer with regionalized headand trunk-inducing ability was further taken up by Spemann
in later experiments that used dorsal lips from early or older
gastrula embryos, which showed that early organizers could
induce a full secondary axis, including a head, whereas older
organizers induced a partial ectopic axis with only trunk and
tail regions ( Hamburger, 1988 ; Spemann, 1936 ). Hence, it
was understood early on that neural induction and specif cation of regional characteristics (patterning) of the induced
neural tissues (head or trunk) were interlinked processes,
and the source of the inducers, the timing of induction, and
the properties of the responding tissues might all inf uence
the outcome. The issue of patterned neural induction along
the embryonic axis was actively pursued in subsequent
studies. Spemann’s students as well as scientists from other
institutions investigated inductive interactions that gave
rise to distinct brain structures or spinal cord, and different
models were put forward to account for the signals involved
in the process ( Doniach, 1993 ; Slack and Tannahill, 1992 ).
In the absence of the identities of the inducing substances,
the quest for the anterior (cranial) and posterior (trunk and
tail) neural inducers persisted to modern days. The advent
of technologies for examining gene expression and manipulating gene functions in recent decades greatly enhanced
our ability to interrogate this classical question with new
rigor, and important insights have been gained into molecular control of both neural induction and neural patterning.
This is especially pertinent using Xenopus, currently the
most popular amphibian model of early development. This
chapter aims to review key aspects of classical works that
inspired different models on anterior-posterior (AP) neural
patterning and discuss several signaling pathways identif ed
using molecular biology approaches that regulate AP neural specifcation. Considerations on a number of remaining
issues regarding AP patterning are also discussed brief y.
5.2. CLASSICAL EXPERIMENTAL EMBRYOLOGY
STUDIES BROUGHT FORTH
DIFFERENT MODELS ON ANTERIORPOSTERIOR NEURAL PATTERNING
Development of structures along the head-to-tail (a.k.a.
anterior-posterior or rostral-caudal) axis in vertebrate
DOI: 10.1201/9781003050230-6
51