Nature Ecology & Evolution
| Volume 7 | October
2023 | 1714–1728
1714
nature ecology & evolution
Article
https://doi.org/10.1038/s41559-023-02170-1
A lamprey neural cell type atlas illuminates
the origins of the vertebrate brain
Francesco Lamanna
1,1 0
, Francisca Hervas-Sotomayor
1,1 0
,
A. Phillip Oel
1,2
, David Jandzik
3,4
, Daniel Sobrido-Cameán
5
,
Gabriel N. Santos-Durán
5
, Megan L. Martik
6,8
, Jan Stundl
6
,
Stephen A. Green
6
, Thoomke Brüning
1
, Katharina Mößinger
1
, Julia Schmidt
1
,
Celine Schneider
1
, Mari Sepp
1
, Florent Murat
1,9
, Jeramiah J. Smith
7
,
Marianne E. Bronner
6
, María Celina Rodicio
5
, Antón Barreiro-Iglesias
5
,
Daniel M. Medeiros
3
, Detlev Arendt
2
& Henrik Kaessmann
1
The vertebrate brain emerged more than ~500 million years ago in
common evolutionary ancestors. To systematically trace its cellular and
molecular origins, we established a spatially resolved cell type atlas of
the entire brain of the sea lamprey—a jawless species whose phylogenetic
position affords the reconstruction of ancestral vertebrate traits—based
on extensive single-cell RNA-seq and in situ sequencing data. Comparisons
of this atlas to neural data from the mouse and other jawed vertebrates
unveiled various shared features that enabled the reconstruction of cell
types, tissue structures and gene expression programs of the ancestral
vertebrate brain. However, our analyses also revealed key tissues and cell
types that arose later in evolution. For example, the ancestral brain was
probably devoid of cerebellar cell types and oligodendrocytes (myelinating
cells); our data suggest that the latter emerged from astrocyte-like
evolutionary precursors in the jawed vertebrate lineage. Altogether, our
work illuminates the cellular and molecular architecture of the ancestral
vertebrate brain and provides a foundation for exploring its diversification
during evolution.
The vertebrate brain is a structurally complex and preeminent organ
because of its central functions in the body. Its most fundamental divi
-
sions are the forebrain (prosencephalon, traditionally divided into the
telencephalon and diencephalon), the midbrain (mesencephalon) and
the hindbrain (rhombencephalon) (Fig.
1a
). This regionalization is
shared across all extant jawed vertebrates and is present even in jawless
vertebrates (that is, the extant cyclostomes: lampreys and hagfishes),
the sister lineage of jawed vertebrates (gnathostomes)
1
(Fig.
1a
), which
have overall less complex brains than jawed vertebrates
2
. While a basic
molecular regionalization has been described for the substantially
simpler central nervous systems (CNSs) of the closest evolutionary
relatives of vertebrates (urochordates and cephalochordates)
3
–
5
, the
anatomical complexity of the four major divisions of the vertebrate
brain evolved in common vertebrate ancestors ~515–645 million years
Received: 23 February 2022
Accepted: 18 July 2023
Published online: 14 September 2023
Check for updates
1
Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany.
2
Developmental Biology Unit, European
Molecular Biology Laboratory, Heidelberg, Germany.
3
Department of Ecology and Evolutionary Biology, University of Colorado Boulder, Boulder, CO,
USA.
4
Department of Zoology, Comenius University, Bratislava, Slovakia.
5
Department of Functional Biology, CIBUS, Faculty of Biology, Universidade de
Santiago de Compostela, Santiago de Compostela, Spain.
6
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena,
CA, USA.
7
Department of Biology, University of Kentucky, Lexington, KY, USA.
8
Present address: Department of Molecular and Cell Biology, University
of California Berkeley, Berkeley, CA, USA.
9
Present address: INRAE, LPGP, Rennes, France.
10
These authors contributed equally: Francesco Lamanna,
Francisca Hervas-Sotomayor.
e-mail:
f.lamanna@zmbh.uni-heidelberg.de
;
f.hervas@zmbh.uni-heidelberg.de
;
h.kaessmann@zmbh.uni-heidelberg.de