Basic mechanisms of morphogenesis during

development

UM Fiúza
Summer School
July 2019
 Developmental biology

zygote
mouse
Sea urchin

zebrafish
Hydra

Starfish Fruit fly

Developmental biology studies how a single cell generates an organism and maintains it
Similarities in embryogenesis across species
(18h)

Ernst Haeckel
 Embryonic development
Maternal control Zygotic control (18h)

Ascidian embryogenesis
Development is driven by patterned cell differentiation and
morphogenesis

Morphogenesis: shape generation

Biologywise.org From P. Lemaire

The animal body axis
 Patterning morphogenesis: organizers

Image source: veteriankey.com

 Signalling and the animal body axis

Speer et al, Cell Reports, 2019

Signalling and the animal body axis

Hyb-Cat ectopic expression

Hobmayer et al, Nature, 2000

 Signalling in development
secreted ligands secreted hormones

receptors

cytoplasm cytoplasm

nucleus nucleus
active gene active gene
expression expression

Cell-cell communication
Bilaterality – patterning two orthogonal body axes by signaling
regulation
The developmental signalling toolkit: regulating cellular activities

Signalling regulated cellular activities

. Growth
. Shape
. Motility
. Differentiation
 Morphogenesis: the importance of cell behaviour

Ascidian development Drosophila development

Guignard and Fiuza et al, BioRxiv, 2017 Dimitri Kromm

Digital representation derived from membrane
imaging, colour coded cell fate
 Cellular mechanisms of morphogenesis

The cellular mechanisms of morphogenesis:

. individual cell shape changes
. cell-cell contact remodelling
. cell death
. growth
 Cellular mechanisms of morphogenesis

The cellular mechanisms of morphogenesis:

. individual cell shape changes
. cell-cell contact remodelling
. cell death
. growth
Individual cell shape changes and morphogenesis: tissue invagination

ventral furrow

Brain folding Drosophila fly Drosophila fly Optic cup

cephalic furrow ventral furrow formation
formation formation
Individual cell shape changes and morphogenesis: tissue invagination
Ascidian endoderm invagination

Lecuit et al, Annual Reviews of Cell Dev Biol, 2011

Individual cell shape changes and morphogenesis: tissue invagination

Ascidian endoderm invagination Drosophila ventral furrow invagination

U.M. Fiuza (Hufnagel lab) D. Kromm (Hufnagel lab)

Gastrulation
Individual cell shape changes and morphogenesis: epiboly

Zebrafish epiboly

Bruce AE, (2015) Developmental Dynamics, 245(3):244-258, DOI: (10.1002/dvdy.24353)

Individual cell shape changes and morphogenesis: epithelial to
mesenchymal transition (EMT)

Michallizi et al (2010) J. of Mammary Gland Biology and Neoplasia, 15(2): 117-134

Molecular drivers of individual cell shape changes: the actomyosin
cytoskeleton and cell adhesion

Letort G, et al. (2015) Dynamic reorganization of the actin cytoskeleton. Martin (2010) Developmental Biology, 341(1):114-125.
F1000Research 4:940
 Cellular mechanisms of morphogenesis

The cellular mechanisms of morphogenesis:

. individual cell shape changes
. cell-cell contact remodelling
. cell death
. growth
Cell-cell contact remodelling and morphogenesis: convergent extension

Cellular mechanisms of intercalation Convergent-extension in Ciona

Keys et al. (2002) Developmental Biology, 246: 329-340

Lecuit et al, Annual Reviews of Cell Dev Biol, 2011

Cell-cell contact remodelling and morphogenesis: Differential Adhesion
Hypothesis (DAH)

4h after incubation 24h after incubation

N-Cadherin (adhesion
molecule) expressed at a
ratio of 2.4:1.
Cells expressing different
levels are differentially
colour labelled
Steinberg (2007) Curr. Op. in Gen. & Dev., 17(4):281-286
Cell-cell contact remodelling and morphogenesis: Differential Adhesion
Hypothesis (DAH)

4h after incubation 24h after incubation

N-Cadherin expression
levels:
Red < Green

Steinberg (2007) Curr. Op. in Gen. & Dev., 17(4):281-286

 Cellular mechanisms of morphogenesis

The cellular mechanisms of morphogenesis:

. individual cell shape changes
. cell-cell contact remodelling
. cell death
. growth
 Programmed cell death in morphogenesis

Limb formation
 Cellular mechanisms of morphogenesis

The cellular mechanisms of morphogenesis:

. individual cell shape changes
. cell-cell contact remodelling
. cell death
. growth
Growth: oriented cell divisions, cell polarity and differential growth

Diaz de la Loza and Thompson (2017), Mechanisms of Development, 144:23-32

Oriented cell divisions mechanisms: PCP and tissue mechanics

Devenport (2014) JCB, 207(1):171 PCP controls tissue

cellular organization
Oriented cell divisions mechanisms: PCP and tissue mechanics

Scarpa et al (2018) Dev. Cell, 47(6):727-740

Growth: unequal cell divisions and cell polarity

Campanale and Hamdoun, Development, 2012

 Patterning development in space and time

Morphogenesis is driven by cell behaviour:

. individual cell shape changes
. cell-cell contact remodelling
. cell death
. growth

Cell fate is regulated by gene expression and different cell fates

can exhibit different characteristic cell behaviours
 Summary and take home messages

Morphogenesis is the process of shape generation during

development and is orchestrated by developmental signalling
induced by organizer regions
Tissue morphogenesis relies on cellular behaviour
The cellular mechanisms of morphogenesis are:
. individual cell shape changes (e.g. invagination, EMT, epiboly)
. cell-cell contact remodelling (e.g. convergent-extension, DAH)
. cell death (e.g. programmed cell death can shape limbs)
. growth (e.g. differential growth and oriented cell divisions)