Jhoanna Rein S.

Duzon
4B4

A. Cellular communication
1. Title: Lateral inhibition and the development of the sensory bristles of the adult peripheral
nervous system of Drosophila
2. Journal Info: Simpson, P. (1990). Lateral inhibition and the development of the sensory bristles
of the adult peripheral nervous system of Drosophila. Development,109(3), 509-519. Retrieved
October 6, 2018, from http://dev.biologists.org/content/develop/109/3/509.full.pdf
3. One to two take home message: The need for a wide diversity of positional identities may be
the reason why neural precursors segregate individually from over a large area of the animal. A
small group of cells is collectively determined and acquires neural potential which then
necessitates a second process, lateral inhibition, whereby cell interactions between the group of
equipotential cells lead to the singling out of one dominant cell that adopts the neural fate.
4. Summary/Findings (10-20 sentences): Cells in the neurectoderm of Drosophila face a choice
between neural and epidermal fates. On the notum of the adult fly, neural cells differentiate sensory
bristles in a precise pattern. Evidence has accumulated that the bristle pattern arises from the spatial
distribution of small groups of cells, proneural clusters, from each of which a single bristle will
result. One class of genes, which includes the genes of the achaete-scute complex, is responsible
for the correct positioning of the proneural clusters. The cells of a proneural cluster constitute an
equivalence group, each of them having the potential to become a neural cell. Only one cell,
however, will adopt the primary, dominant, neural fate. This cell is selected by means of cellular
interactions between the members of the group, since if the dominant cell is removed, one of the
remaining, epidermal, cells will switch fates and become neural. The dominant cell prevents the
other cells of the group from becoming neural by a phenomenon known as lateral inhibition. They,
then, adopt the secondary, epidermal, fate. A second class of genes, including the gene shaggy and
the neurogenic genes mediate this process. There is some evidence that a proneural cluster is
composed of a small number of cells, suggesting a contact-based mechanism of communication.
B. Apoptosis
1. Title: Role of BMP-2 and OP-1 (BMP-7) in programmed cell death and skeletogenesis during
chick limb development
2. Journal Info: Macias, D., Ganan, Y., Sampath, T., Piedra, M., Ros, M., & Hurle, J. (1997). Role
of BMP-2 and OP-1 (BMP-7) in programmed cell death and skeletogenesis during chick limb
development. Development,124(6), 1109-1117. Retrieved October 6, 2018, from
http://dev.biologists.org/content/develop/124/6/1109.full.pdf
3. One to two take home message: Implantation of BMP-beads in different regions and stages of
the developing limb was always followed by cell death in the undifferentiated limb mesenchyme.
4. Summary/Findings (10-20 sentences): Bone Morphogenetic Protein 2 (BMP-2) and Osteogenic
Protein 1 (OP-1, also termed BMP-7) are members of the transforming growth factor β
superfamily. In the present study, we have analyzed the effects of administering them locally at
different stages and locations of the chick limb bud using heparin beads as carriers. Our results
show that these BMPs are potent apoptotic signals for the undifferentiated limb mesoderm but not
for the ectoderm or the differentiating chondrogenic cells. In addition, they promote intense radial
growth of the differentiating cartilages and disturb the formation of joints accompanied by
alterations in the pattern of Indian hedgehog and ck-erg expression. Interestingly, the effects of
these two BMPs on joint formation were found to be different. While the predominant effect of
BMP-2 is alteration in joint shape, OP1 is a potent inhibitory factor for joint formation. In situ
hybridizations to check whether this finding was indicative of specific roles for these BMPs in the
formation of joints revealed a distinct and complementary pattern of expression of these genes
during the formation of the skeleton of the digits. While Op-1 exhibited an intense expression in
the perichondrium of the developing cartilages with characteristic interruptions in the zones of
joint formation, Bmp-2 expression was a positive marker for the articular interspaces. These data
suggest that, in addition to the proposed role for BMP-2 and OP-1 in the establishment of the
anteroposterior axis of the limb, they may also play direct roles in limb morphogenesis: (i) in
regulating the amount and spatial distribution of the undifferentiated prechondrogenic
mesenchyme and (ii) in controlling the location of the joints and the diaphyses of the cartilaginous
primordia of the long bones once the chondrogenic aggregates are established.

C. Induction
1. Title: Features of embryonic induction
2. Journal Info: Jacobson, A. G., & Sater, A. K. (1988). Features of embryonic
induction. Development,104(3), 341-359. Retrieved October 6, 2018, from
http://dev.biologists.org/content/develop/104/3/341.full.pdf
3. One to two take home message: Embryonic induction consists of an interaction between
inducing and responding tissues that brings about alterations in the developmental pathway of the
responding tissue
4. Summary/Findings (10-20 sentences): The patterned distribution of different organs in the
amphibian embryo begins with the establishment of two domains, the animal and vegetal regions,
that differ in developmental potency. Differences amplify as inductive interactions occur across
boundaries between areas of different potency. Embryonic induction establishes a temporally and
spatially dynamic area of developmental potency - a morphogenetic field. The final arrangement
and differentiation of cell types within the field emerge from subsequent interactions occurring
primarily within the field. These principles are illustrated in a review of the induction of the lens
and the heart. Recent studies show that the induction of the lens of the eye and the induction of the
heart begin early in development. Most of lens inductions occurs before the formation of the optic
vesicle, and the heart appears to be part of a complex of dorsal structures whose formation is
dependent upon the establishment of the dorsoventral axis. Suppressive as well as inductive tissue
interactions occur during the determination of both of these organs, affecting their position and
time of appearance. The complex processes of induction defined by the past nine decades of
experimental work present many challenging questions that can now be addressed, especially in
terms of the molecular events, cellular behaviour and regulatory physiology of the responding
tissue.

D. Morphogenesis
1. Title: Variations in basement membrane mechanics are linked to epithelial morphogenesis
2. Journal Info: Chlasta, J., Milani, P., Runel, G., Duteyrat, J., Arias, L., Lamiré, L., . . . Grammont,
M. (2017). Variations in basement membrane mechanics are linked to epithelial
morphogenesis. Development,144(23), 4350-4362. Retrieved October 6, 2018, from
http://dev.biologists.org/content/develop/144/23/4350.full.pdf
3. One to two take home message: BMs are known to assist epithelial cells during morphogenetic
processes by providing a mechanical support to resist the contractile forces emanating from
epithelial cells, by constraining locally or globally the expansion of tissues, by regulating growth
factor delivery, and by regulating cell adhesion and signalling of BM receptors.
4. Summary/Findings (10-20 sentences): Extracellular matrices (ECMs) are essential for the
development of multicellular eukaryotic organisms (Ozbek et al., 2010). ECM proteins form a
network that fills spaces between organs and mechanically supports them (Hynes and Naba,
2012).The regulation of morphogenesis by the basement membrane (BM) may rely on changes in
its mechanical properties. To test this, we developed an atomic force microscopy-based method to
measure BM mechanical stiffness during two key processes in Drosophila ovarian follicle
development. First, follicle elongation depends on epithelial cells that collectively migrate,
secreting BM fibrils perpendicularly to the anteroposterior axis. Our data show that BM stiffness
increases during this migration and that fibril incorporation enhances BM stiffness. In addition,
stiffness heterogeneity, due to oriented fibrils, is important for egg elongation. Second, epithelial
cells change their shape from cuboidal to either squamous or columnar. We prove that BM softens
around the squamous cells and that this softening depends on the TGFβ pathway. We also
demonstrate that interactions between BM constituents are necessary for cell flattening.
Altogether, these results show that BM mechanical properties are modified during development
and that, in turn, such mechanical modifications influence both cell and tissue shapes.
E. Differentiation
1. Title: Neural differentiation, selection and transcriptomic profiling of human neuromesodermal
progenitor-like cells in vitro
2. Journal Info: Verrier, L., Davidson, L., Gierliński, M., Dady, A., & Storey, K. (2018). Neural
differentiation, selection and transcriptomic profiling of human neuromesodermal progenitor-like
cells in vitro. Development,145(16). Retrieved October 6, 2018, from
http://dev.biologists.org/content/develop/145/16/dev166215.full.pdf
3. One to two take home message: Most in vitro differentiation protocols are informed by our
understanding of how the cell type of interest is generated during embryonic development.
4. Summary/Findings (10-20 sentences): Robust protocols for directed differentiation of human
pluripotent cells are required to determine whether mechanisms operating in model organisms are
relevant to our own development. Recent work in vertebrate embryos has identified
neuromesodermal progenitors as a bipotent cell population that contributes to paraxial mesoderm
and spinal cord. However, precise protocols for in vitro differentiation of human spinal cord
progenitors are lacking. Informed by signalling in amniote embryos, we show here that transient
dual-SMAD inhibition, together with retinoic acid (dSMADi-RA), provides rapid and
reproducible induction of human spinal cord progenitors from neuromesodermal progenitor-like
cells. Using CRISPR-Cas9 to engineer human embryonic stem cells with a GFP-reporter for
neuromesodermal progenitor-associated gene Nkx1.2 we facilitate selection of this cell population.
RNA-sequencing was then used to identify human and conserved neuromesodermal progenitor
transcriptional signatures, to validate this differentiation protocol and to reveal new
pathways/processes in human neural differentiation. This optimised protocol, novel reporter line
and transcriptomic data are useful resources with which to dissect molecular mechanisms
regulating human spinal cord generation and allow the scaling-up of distinct cell populations for
global analyses, including proteomic, biochemical and chromatin interrogation.