The_Scientist_-_December_2018

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56 THE SCIENTIST | the-scientist.com


PROFILE

tion, and I got a non-tenure track one where I had to raise my
own salary by writing grants,” says Bronner. In the 1980s, as
is the case today, it was unusual to start a laboratory straight
out of graduate school. “I was 27 and naive about how hard
this could be,” she says. “In a way, I was doing a postdoc with
myself! I had no real mentors in graduate school or when I
started my lab.”
Fortunately, Bronner received funding for her grant pro-
posals and could continue her studies of neural crest cell fate,
doing most of the experiments herself. She finally was offered
a tenure track position at UC Irvine in 1985. In a study pub-
lished in 1986, on which she was the sole author, Bronner
showed that, rather than migrating around body segment
structures in the early embryo, as had been thought, neu-
ral crest cells were actually migrating through half of these
structures, suggesting there were repulsive cues that guided
their path. A year later, Bronner was promoted to associate
professor with tenure—on the same day that her daughter,
Paige, was born.
Bronner’s first truly exciting result in the lab, she says,
came in 1988, in collaboration with Fraser. They labeled a
neural crest precursor cell in the chicken embryo using dye
and an adaptation of an electrophysiological technique used
for recording neural activity and saw that individual neural
crest cells could give rise to multiple cell types, demonstrat-
ing that they were multipotent. “The cells were thought to be
multipotent in vitro, but this was the first time it was shown
in the embryo, suggesting they were stem cells,” Bronner says.
A quarter of a century later, a paper published in 2015 showed
a similar result using newer cell lineage tracing technology in
mice. “I was very pleased,” she says.
While Bronner’s lab later used mice and other models to
study embryogenesis, the chicken embryo is still proving to
be a useful system. “Chicken embryos are better than mouse
embryos to study neural crest biology,” she says. “They are
much more accessible because the chick develops in an egg
outside of the mom.” Mouse embryo development also has
some unusual features at early stages, whereas the chick
embryo is more similar to a human in terms of neural crest
development. CRISPR and other genomic tools, she adds, are
also opening up new insights in the field, allowing research-
ers to create transient knockouts, bypassing the need to wait
through long chicken generation times.

EXPANDING HER FOOTPRINT
As her success continued, Bronner’s lab grew. In 1990, she
became a full professor—the same year her son, Ryan, was
born. “Each time I had a kid, I got promoted,” she says. In
1996, Bronner moved her lab to Caltech.
There, her team studied the origin of neural crest cells in
the embryo. Mark Selleck, then a postdoc, and graduate stu-
dent Mary Dickinson found that the interaction between a
piece of neural tube tissue, which is normally distinct from

the neural crest, and cells that normally become skin cells in
vivo results in the formation of neural crest cells. “This was an
early example showing that neural crest cells were an induced
cell type,” says Bronner.
This result led the lab on a journey to identify what mol-
ecule induced the neural crest cells to form. Examining the
genetics of neural crest induction, then-postdoc Laura Gam-
mill performed a transcriptome analysis, identifying genes
involved in neural crest development and migration, and
then-postdoc Martín García-Castro identified Wnt as one of
the inducers in the chick embryo, results reported in 2002.
Four years later, Bronner and her lab members found that
induction of the neural crest begins much earlier in devel-
opment than previously thought, during gastrulation—when
the single-layered blastula reorganizes into the multilayered
gastrula. In 2007, then-postdoc Tatjana Sauka-Spengler
found that this was a broader phenomenon, with experi-
ments showing that the neural crest gene regulatory pro-
gram was largely conserved throughout vertebrate evolution.

But not all neural crest cells are the same—only those aris-
ing in the head can form facial cartilage and bone. In fact,
Bronner’s postdoc, Marcos Simoes-Costa, recently found that
just three genes are sufficient to endow cranial neural crest
cells with this ability. “Amazingly, this cranial neural crest pro-
gram can be transplanted to other neural crest populations to
reprogram different parts of the embryo,” Bronner says.
Bronner recalls that she and Simoes-Costa “got together
almost every day over coffee to talk about these experiments.”
They were planning every step of the study and “what makes
the most sense to efficiently get the right answer,” she says.
Such intensive mentoring is one of the most important aspects
of Bronner’s work, she adds. “I didn’t have anyone to help guide
me through this career, and I think from what I learned through
brute force, I can help by advising people,” she explains. “My
job is to give people the tools to be the best scientists that they
can be and to accentuate their specific skills.”
Bronner’s lab is still studying the mechanism of neural crest
cell induction and its underlying gene regulation. Just a few
months ago, postdocs Michael Piacentino and Erica Hutchins
identified molecules that downregulate bone morphogenetic
protein and Wnt to intermediate levels that are crucial for the
induction of the neural crest and initiation of the cells’ migra-
tion. “We keep learning more and more,” Bronner says, “and
coming back to the same questions over decades.”g

My job is to give people the tools to be
the best scientists that they can be and to
accentuate their specific skills.
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