The Scientist - USA (2019-12)

innervation from transplanted tissue

or organs can be greatly augmented—

including improvement of vision from

eyes graft ed into a blind Xenopus tad-

pole’s flank—by using zolmitriptan, a

clinically approved serotonin receptor

agonist, to control how transplanted

cells migrate and extend in new envi-

ronments ( npj Regen Med, 2:8, 2017).

We hope that discoveries like this could

eventually lead to improved organ

transplantation outcomes in humans.

Work on the biophysics of how organ

shape, size, and location are specified dur-

ing embryogenesis has also led to a new

understanding of the cause of some birth

defects and to the development of strate-

gies to repair them in vivo. Allen Center

scientists have rescued severe develop-

mental brain damage in Xenopus tadpoles

using relatively simple interventions that

restore the endogenous bioelectric pattern

guiding embryonic cells building the brain

(Nat Commun, 9:998, 2018). Although

many steps remain in translating these

findings into treatments of human birth

defects, this proof-of-principle work sug-

gests a roadmap toward more bioelectric-

targeting drugs, or electroceuticals, for

modifying complex structures in vivo.

This approach could also have

applications in the field of regenerative

biology. While tremendous progress has

been made in creation of artificial limbs,

the ideal solution would be to regener-

ate a patient’s lost hand, arm, foot, or leg

from his/her own endogenous cells. For

example, providing a growth stimulus

(such as a cocktail of drugs that target

ion channels to create an embryonic- like

bioelectric signal for limb formation)

and an environment conducive to new

growth has been enabled by a device—

created by David Kaplan’s laboratory

at Tufts University—that is attached

to the stump resulting from a hind-leg

amputation of an adult frog (Cell Rep,

25:P1593–609.E7, 2019). Just 24 hours

of this treatment induced more than a

year of subsequent tissue growth at the

amputation site.

The Allen Discovery Center’s empha-

sis on the biophysics of anatomical con-

trol has yielded many resources to enable

other labs to work on these questions

with us. The conceptual tools, molecular

reagents, model animals, and software we

have developed to approach dynamic con-

trol problems at different levels of biology

are all freely available to researchers in the

field. Our core mission is to uncover and

exploit the computational layer between

the genome and resulting anatomy, to

impact not only regenerative biomedicine,

but also the synthetic morphology and pro-

gramming of artificial living machines. g

Joshua Finkelstein is deputy director of

the Allen Discovery Center at Tufts Uni-

versity, Kelly McLaughlin is a principal

investigator at the center, and Michael

Levin is the center’s director.

*Weller, MG, Analytical Chemistry
Insights:11, 21-27 (2016).
Antibodies shown: CD3E (A700-016) &
CD20 (A500-017A)
©2019 Bethyl Laboratories, Inc.
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